• 主题
高级搜索  >
历史搜索 清空历史

您现在的位置：首页>美国卫生研究院文献>American Journal of Physiology - Heart and Circulatory Physiology

期刊信息

  • 期刊名称：

    -

  • 刊频： Twice monthly, Feb. 2012-
  • NLM标题： Am J Physiol Heart Circ Physiol
  • iso缩写： -
  • ISSN： -

年度选择

更多>>

  • 排序：
  • 显示：
  • 每页：
全选（0）
<8/12>
共227条结果
  • 1.

    【2hr】Involvement of ROCK-mediated endothelial tension development in neutrophil-stimulated microvascular leakage

    包量

    机译 ROCK介导的内皮细胞张力发展参与中性粒细胞刺激的微血管渗漏
    摘要：Neutrophil-induced coronary microvascular barrier dysfunction is an important pathophysiological event in heart disease. Currently, the precise cellular and molecular mechanisms of neutrophil-induced microvascular leakage are not clear. The aim of this study was to test the hypothesis that rho kinase (ROCK) increases coronary venular permeability in association with elevated endothelial tension. We assessed permeability to albumin (Pa) in isolated porcine coronary venules and in coronary venular endothelial cell (CVEC) monolayers. Endothelial barrier function was also evaluated by measuring transendothelial electrical resistance (TER) of CVEC monolayers. In parallel, we measured isometric tension of CVECs grown on collagen gels. Transference of constitutively active (ca)-ROCK protein into isolated coronary venules or CVEC monolayers caused a significant increase in Pa and decreased TER in CVECs. The ROCK inhibitor Y-27632 blocked the ca-ROCK-induced changes. C5a-activated neutrophils (106/ml) also significantly elevated venular Pa, which was dose-dependently inhibited by Y-27632 and a structurally distinct ROCK inhibitor, H-1152. In CVEC monolayers, activated neutrophils increased permeability with a concomitant elevation in isometric tension, both of which were inhibited by Y-27632 or H-1152. Treatment with ca-ROCK also significantly increased CVEC monolayer permeability and isometric tension, coupled with actin polymerization and elevated phosphorylation of myosin regulatory light chain on Thr18/Ser19. The data suggest that during neutrophil activation, ROCK promotes microvascular leakage in association with actin-myosin-mediated tension development in endothelial cells.
  • 2.

    【2hr】Persistent splanchnic hyperemia during upright tilt in postural tachycardia syndrome

    包量

    机译 姿势性心动过速综合征直立倾斜期间持续的内脏充血
    摘要：Previous investigations have allowed for stratification of patients with postural tachycardia syndrome (POTS) on the basis of peripheral blood flow. One such subset, comprising “normal-flow POTS” patients, is characterized by normal peripheral resistance and blood volume in the supine position but thoracic hypovolemia and splanchnic blood pooling in the upright position. We studied 32 consecutive 14- to 22-yr-old POTS patients comprising 13 with low-flow POTS, 14 with normal-flow POTS, and 5 with high-flow POTS and 12 comparably aged healthy volunteers. We measured changes in impedance plethysmographic (IPG) indexes of blood volume and blood flow within thoracic, splanchnic, pelvic (upper leg), and lower leg regional circulations in the supine posture and during incremental tilt to 20°, 35°, and 70°. We validated IPG measures of thoracic and splanchnic blood flow against indocyanine green dye-dilution measurements. We validated IPG leg blood flow against venous occlusion plethysmography. Control subjects developed progressive vasoconstriction with incremental tilt. Splanchnic blood flow was increased in the supine position in normal-flow POTS, despite marked peripheral vasoconstriction, and did not change during incremental tilt, producing progressive splanchnic hypervolemia. Absolute hypovolemia was present in low-flow POTS, all supine flows and volumes were reduced, there was no vasoconstriction with tilt in all segments, and segmental volumes tended to increase uniformly throughout tilt. Lower body (pelvic and leg) flows were increased in high-flow POTS at all angles, with consequent lower body hypervolemia during tilt. Our main finding is selective and maintained orthostatic splanchnic vasodilation in normal-flow POTS, despite marked peripheral vasoconstriction in these same patients. Local splanchnic vasoregulatory factors may counteract vasoconstriction and venoconstriction in these patients. Lower body vasoconstriction in high-flow POTS was abnormal, and vasoconstriction in low-flow POTS was sustained at initially elevated supine levels.
  • 3.

    【2hr】MACROMOLECULE PERMEABILITY OF IN SITU AND EXCISED RODENT SKELETAL MUSCLE ARTERIOLES AND VENULES.

    包量

    机译 原位和异常啮齿动物骨骼动荡和静脉的大分子渗透率。
    摘要：In microvessels, acute inflammation is typified by an increase in leukocyte-endothelial cell interactions culminating in leukocyte transmigration into the tissue, and increased permeability to water and solutes, resulting in tissue edema. The goal of this study was to establish a method to quantify solute permeability (Ps) changes in microvessels in intact predominantly blood perfused networks in which leukocyte transmigratory behavior could be precisely described using established paradigms. We used intravital confocal microscopy to measure solute (BSA) flux across microvessel walls, hence Ps. The quantitative fluorescence approach of Huxley et al (Am. J. Physiol. 252:H188–H197,1987) was adapted to the imaged confocal tissue slice in which the fluorescent source volume and source surface area of the microvessel were restricted to the region of vessel that was contained within the imaged confocal tissue section. Ps measurements were made in intact cremaster muscle microvasculature of anesthetized mice and compared to measurements of Ps made in isolated rat skeletal muscle microvessels. Mouse arteriolar Ps was 9.9±1.1 × 10−7cm.sec−1 (n=16), which was not different from 8.4±1.3 × 10−7cm.sec−1 (n=6) in rat arterioles. Values in venules were significantly (p<.05) higher: 44.4±7.9 × 10−7cm.sec−1 (n=14) in mice and 25.0±3.7 × 10−7cm.sec−1 in rats. Convective coupling was estimated to contibute <10% to the measured Ps in both microvessel types and both animal models. We conclude that this approach provides an appropriate quantification of Ps in the intact microvasculature, and that arteriolar Ps, while lower than in venules, is nevertheless consistent with arterioles being a significant source of interstitial protein.
  • 4.

    【2hr】Critical mass hypothesis revisited: role of dynamical wave stability in spontaneous termination of cardiac fibrillation

    包量

    机译 临界质量假说再访：动态波稳定性在心律失常自发终止中的作用
    • 作者：Zhilin Qu
    • 刊名：American Journal of Physiology - Heart and Circulatory Physiology
    • 2006年第1期
    摘要：The tendency of atrial or ventricular fibrillation to terminate spontaneously in finite-sized tissue is known as the critical mass hypothesis. Previous studies have shown that dynamical instabilities play an important role in creating new wave breaks that maintain cardiac fibrillation, but its role in self-termination, in relation to tissue size and geometry, is not well understood. This study used computer simulations of two- and three-dimensional tissue models to investigate qualitatively how, in relation to tissue size and geometry, dynamical instability affects the spontaneous termination of cardiac fibrillation. The major findings are as follows: 1) Dynamical instability promotes wave breaks, maintaining fibrillation, but it also causes the waves to extinguish, facilitating spontaneous termination of fibrillation. The latter effect predominates as dynamical instability increases, so that fibrillation is more likely to self-terminate in a finite-sized tissue. 2) In two-dimensional tissue, the average duration of fibrillation increases exponentially as tissue area increases. In three-dimensional tissue, the average duration of fibrillation decreases initially as tissue thickness increases as a result of thickness-induced instability but then increases after a critical thickness is reached. Therefore, in addition to tissue mass and geometry, dynamical instability is an important factor influencing the maintenance of cardiac fibrillation.
  • 5.

    【2hr】CONTRIBUTIONS OF ASTROCYTES AND CO TO PIAL ARTERIOLAR DILATION TO GLUTAMATE IN NEWBORN PIGS

    包量

    机译 新生猪中星形胶质细胞和一氧化碳对颈动脉缩窄的影响
    摘要：Astrocytes can act as intermediaries between neurons and cerebral arterioles to regulate vascular tone in response to neuronal activity. Release of glutamate from presynaptic neurons increases blood flow to match metabolic demands. CO is a gasotransmitter that can be related to neural function and blood flow regulation in the brain. The present study addresses the hypothesis that glutamatergic stimulation promotes perivascular astrocyte CO production and pial arteriolar dilation in the newborn brain. Experiments used anesthetized newborn pigs with closed cranial windows, piglet astrocytes and cerebrovascular endothelial cells in primary culture, and immunocytochemical visualization of astrocytic markers. Pial arterioles and arteries of newborn pigs are ensheathed by astrocytes visualized by glial fibrillary acidic protein (GFAP) staining. Treatment (2h) of astrocytes in culture with L-2-alpha aminoadipic acid (L-AAA), followed by 14 hr in toxin free medium, dose-dependently increased cell detachment suggesting injury. Conversely, 16h of continuous exposure to L-AAA caused no decrease in endothelial cell attachment. In vivo, topical L-AAA (2mM, 5h) disrupted the cortical glia limitans histologically. Such treatment also eliminated pial arteriolar dilation to the astrocyte-dependent dilator, ADP, and to glutamate, but not to isoproterenol or CO. Glutamate stimulated CO production by the brain surface that also was abolished following L-AAA. In contrast, tetrodotoxin blocked dilation to NMDA, but not to glutamate, isoproterenol, or CO, or the glutamate-induced increase in CO. The concurrent loss of CO production and pial arteriolar dilation to glutamate following astrocyte injury suggests astrocytes may employ CO as a gasotransmitter for glutamatergic cerebrovascular dilation.
  • 6.

    【2hr】Role of diastolic properties in the transition to failure in a mouse model of cardiac dilatation

    包量

    机译 舒张特性在心脏扩张小鼠模型向衰竭转变中的作用
    摘要：Although the physiological states of hypertrophic remodeling and congestive heart failure have been intensively studied, less is known about the transition from one to the other. The use of genetically engineered murine models of heart failure has proven valuable in characterizing the progression of remodeling and its ultimate decompensation to failure. Mice deficient in the cytoskeletal muscle LIM-only protein (MLP) are known to present with a clinical picture of dilated cardiomyopathy and transition to failure as adults. Longitudinal high-field magnetic resonance (MR) cardiac imaging provided a time course of remodeling where an improvement in ejection fraction and stroke volume (15- vs. 31-wk MLP−/− mice; P < 0.0001) was temporally concurrent with an abrupt phase of end-diastolic chamber dilatation. Hemodynamic analysis conducted throughout that dilatation phase showed improved ratio of maximum first derivative of pressure to end-diastolic pressure (dP/dtmax/EDP; 15- vs. 31-wk MLP−/− mice; P < 0.0005), ratio of minimum first derivative of pressure to EDP (dP/dtmin/EDP; 15- vs. 31-wk MLP−/− mice; P < 0.003), and developed pressure (15- vs. 31-wk MLP−/− mice; P < 0.0001) levels in the MLP−/− mice. Computational modeling techniques were used to estimate the EDP volume relationship, revealing that although MLP hearts possess a stiffer stress-strain relation, chamber compliance increased as a function of dilatation. This detailed physiological characterization during a phase of rapid anatomical remodeling suggests that systolic function in the MLP−/−mice may temporarily improve as a result of alterations in chamber compliance, which are mediated by dilatation. In turn, a balance may exist between exploiting the Frank-Starling mechanism and altering chamber compliance that maintains function in the absence of hypertrophic growth. Though initially compensatory, this process may exhaust itself and consequently transition to a maladaptive course.
  • 7.

    【2hr】Adenosine A2A receptor modulation of juvenile female rat skeletal muscle microvessel permeability

    包量

    机译 腺苷A2A受体调节雌性大鼠骨骼肌微血管通透性
    摘要：Little is known of the regulation of skeletal muscle microvascular exchange under resting or stimulating conditions. Adenosine (ADO) levels in skeletal muscle increase during physiological (exercise) and pathological (hypoxia, inflammation, and ischemia) conditions. Later stages of these pathologies are characterized by the loss of vascular barrier integrity. This study focused on determining which ADO receptor mediates the robust reduction in microvessel permeability to rat serum albumin (PsRSA) observed in juvenile female rats. In microvessels isolated from abdominal skeletal muscle, ADO suffusion induced a concentration-dependent reduction in arteriolar [log(IC50) = −9.8 ± 0.2 M] and venular [log(IC50) = −8.4 ± 0.2 M] PsRSA. RT-PCR and immunoblot analysis demonstrated mRNA and protein expression of ADO A1, A2A, A2B, and A3 receptors in both vessel types, and immunofluorescence assay revealed expression of the four subtype receptors in the microvascular walls (endothelium and smooth muscle). PsRSA responses of arterioles and venules to ADO were blocked by 8-(p-sulphophenyl)theophylline, a nonselective A1 and A2 antagonist. An A2A agonist, , was more potent than the A1 agonist, cyclopentyladenosine, or the most-selective A2B agonist, 5′-(N-ethylcarboxamido)adenosine. The ability of or ADO to reduce PsRSA was abolished by the A2A antagonist, ZM241385. An adenylyl cyclase inhibitor, SQ22536, blocked the permeability response to ADO. In aggregate, these results demonstrate that, in juvenile females (before the production of the reproductive hormones), ADO enhances skeletal muscle arteriole and venule barrier function predominantly via A2A receptors using activation of adenylyl cyclase-signaling mechanisms.
  • 8.

    【2hr】TNF-α ACTIVATION OF ARTERIOLES AND VENULES ALTERS THE DISTRIBUTION AND LEVELS OF ICAM-1 AND AFFECTS LEUKOCYTE-ENDOTHELIAL CELL INTERACTIONS

    包量

    机译 TNF-α激活小动脉和静脉，改变ICAM-1的水平和水平，影响白细胞与内皮细胞的相互作用
    摘要：The observation that leukocyte-endothelial cell (EC) interactions are localized to specific regions on the microvessel wall suggests that adhesion molecule distribution is not uniform. We investigated ICAM-1 distribution and leukocyte-EC interactions in blood perfused microvessels (< 80 μm) in cremaster muscle of anesthetized mice, using intravital confocal microscopy and immunofluorescent labeling. Variability of ICAM-1 expression directly determines leukocyte adhesion distribution within the venular microcirculation, and contributes to leukocyte rolling in arterioles during inflammation. The number of rolling interactions increased with ICAM-1 intensity (r2=0.69, p<0.05) and rolling velocity was lower in regions of higher ICAM-1 intensity. In controls, venular ICAM-1 expression was approximately two fold higher than in arterioles. Following TNF-α treatment, ICAM-1 expression was significantly increased, 2.8±0.2 fold in arterioles and 1.7±0.2 fold in venules (P<0.05). ICAM-1 expression on activated arteriolar ECs only reached the level of control venular ICAM-1. Arteriolar but not venular ECs underwent redistribution of ICAM-1 among cells; some cells increased and some decreased ICAM-1 expression, magnifying the variability of ICAM-1. TNF-α treatment increased the length of bright fluorescent regions per unit vessel length (42%, control; 70%, TNF-α) along the arteriolar wall, whereas no significant change was observed in venules (60%, control; 63%, TNF-α). The spatial distribution and expression levels of adhesion molecules in the microcirculation determine the timing and placement of leukocyte interactions, hence significantly impact the inflammatory response. That arteriolar ECs respond to TNF-α by upregulation of ICAM-1, although in a different way compared to venules, suggests an explicit role for arterioles in inflammatory responses.
  • 9.

    【2hr】Altered contractility and [Ca2+]i homeostasis in phospholemman-deficient murine myocytes: Role of Na+/Ca2+ exchange

    包量

    机译 磷酸lemman缺陷型鼠心肌细胞中收缩力和[Ca2 +] i稳态的改变：Na + / Ca2 +交换的作用
    摘要：Phospholemman (PLM), a 72-amino acid sarcolemmal protein, has been shown to regulate contractility and Ca2+ homeostasis in cardiac myocytes, likely via its modulatory influence on Na+/Ca2+ exchanger and Na+-K+-ATPase. In this study, we characterized excitation-contraction coupling in myocytes isolated from PLM-deficient mice back-bred to a pure congenic C57BL/6 background. There were no differences in cell length, cell width and whole cell capacitance between wild-type and PLM-null myocytes. Compared to wild-type myocytes, Western blots indicated total absence of PLM but no changes in Na+/Ca2+ exchanger, sarcoplasmic reticulum (SR) Ca2+-ATPase, α1-subunit of Na+-K+-ATPase and calsequestrin levels in PLM-null myocytes. At 5mM extracellular [Ca2+] concentration ([Ca2+]o), contraction and cytosolic [Ca2+] ([Ca2+]i) transient amplitudes and SR Ca2+ contents in PLM-null myocytes were significantly (p<0.0004) higher than wild-type myocytes. At 0.6 mM [Ca2+]o, however, contraction and [Ca2+]i transient amplitudes and SR Ca2+ contents were significantly lower in PLM-null than wild-type myocytes. At 1.8 mM [Ca2+]o, the differences in contraction and [Ca2+]i transient amplitudes were no longer apparent. This pattern of contractile and [Ca2+]i transient abnormalities in PLM-null myocytes mimics that observed in adult rat myocytes overexpressing the cardiac Na+/Ca2+ exchanger. Indeed, we have previously reported that Na+/Ca2+ exchange currents were higher in PLM-null myocytes. Activation of protein kinase A resulted in increased inotropy such that there were no longer any contractility differences between the stimulated wild-type and PLM-null myocytes. Protein kinase C stimulation resulted in decreased contractility in both wild-type and PLM-null myocytes. Resting membrane potential and action potential amplitudes were similar, but action potential duration was much prolonged (p<0.04) in PLM-null myocytes. Whole cell Ca2+ current densities were similar between wild-type and PLM-null myocytes, as were the fast and slow inactivation time constants. We conclude that a major function of PLM is regulation of cardiac contractility and Ca2+ fluxes, likely by modulating Na+/Ca2+ exchange activity.
  • 10.

    【2hr】Functional significance of differential eNOS translocation

    包量

    机译 差异eNOS易位的功能意义
    摘要：Nitric oxide (NO) regulates flow and permeability. ACh and platelet-activating factor (PAF) lead to endothelial NO synthase (eNOS) phosphorylation and NO release. While ACh causes only vasodilation, PAF induces vasoconstriction and hyperpermeability. The key differential signaling mechanisms for discriminating between vasodilation and hyperpermeability are unknown. We tested the hypothesis that differential translocation may serve as a regulatory mechanism of eNOS to determine specific vascular responses. We used ECV-304 cells permanently transfected with eNOS-green fluorescent protein (ECVeNOS-GFP) and demonstrated that the agonists activate eNOS and reproduce their characteristic endothelial permeability effects in these cells. We evaluated eNOS localization by lipid raft analysis and immunofluorescence microscopy. After PAF and ACh, eNOS moves away from caveolae. eNOS distributes both in the plasma membrane and Golgi in control cells. ACh (10−5 M, 10−4 M) translocated eNOS preferentially to the trans-Golgi network (TGN) and PAF (10−7 M) preferentially to the cytosol. We suggest that PAF-induced eNOS translocation preferentially to cytosol reflects a differential signaling mechanism related to changes in permeability, whereas ACh-induced eNOS translocation to the TGN is related to vasodilation.
  • 11.

    【2hr】Transcription factor CHF1/Hey2 suppresses cardiac hypertrophy through an inhibitory interaction with GATA4

    包量

    机译 转录因子CHF1 / Hey2通过与GATA4的抑制性相互作用抑制心脏肥大
    摘要：Pathological cardiac hypertrophy is considered a precursor to clinical heart failure. Understanding the transcriptional regulators that suppress the hypertrophic response may have profound implications for the treatment of heart disease. We report the generation of transgenic mice that overexpress the transcription factor CHF1/Hey2 in the myocardium. In response to the α-adrenergic agonist phenylephrine, they show marked attenuation in the hypertrophic response compared with wild-type controls, even though blood pressure is similar in both groups. Isolated myocytes from transgenic mice demonstrate a similar resistance to phenylephrine-induced hypertrophy in vitro, providing further evidence that the protective effect of CHF1/Hey2 is mediated at the myocyte level. Induction of the hypertrophy marker genes ANF, BNP, and β-MHC in the transgenic cells is concurrently suppressed in vivo and in vitro, demonstrating that the induction of hypertrophy-associated genes is repressed by CHF1/Hey2. Transfection of CHF1/Hey2 into neonatal cardiomyocytes suppresses activation of an ANF reporter plasmid by the transcription factor GATA4, which has previously been shown to activate a hypertrophic transcriptional program. Furthermore, CHF1/Hey2 binds GATA4 directly in coimmunoprecipitation assays and inhibits the binding of GATA4 to its recognition sequence within the ANF promoter. Our findings demonstrate that CHF1/Hey2 functions as an antihypertrophic gene, possibly through inhibition of a GATA4-dependent hypertrophic program.
  • 12.

    【2hr】COX-2 contributes to the maintenance of flow-induced dilation in arterioles of eNOS-knockout mice

    包量

    机译 COX-2有助于维持eNOS基因敲除小鼠小动脉中的血流诱导的扩张
    摘要：Our previous studies demonstrated that, in gracilis muscle arterioles of male mice deficient in the gene for endothelial nitric oxide synthase (eNOS), flow-induced dilation (FID) is mediated by endothelial PGs. Thus the present study aimed to identify the specific isoform of cyclooxygenase (COX) responsible for the compensatory mediation of FID in arterioles of eNOS-knockout (KO) mice. Experiments were conducted on gracilis muscle arterioles of male eNOS-KO and wild-type (WT) mice. Basal tone and magnitude of FID of arterioles were comparable in the two strains of mice. A role for COX isoforms in the mediation of the responses was assessed by use of valeryl salicylate (3 mM) and NS-398 (10 µM), inhibitors of COX-1 and COX-2, respectively. In eNOS-KO arterioles, valeryl salicylate or NS-398 alone inhibited FID (at maximal flow rate) by ~51% and ~58%, respectively. Administration of both inhibitors eliminated the dilation. In WT arterioles, inhibition of COX-2 did not significantly affect FID, whereas inhibition of COX-1 decreased the dilation by ~57%. The residual portion of the response was abolished by additional administration of Nω-nitro-l-arginine methyl ester. Western blot analysis indicated a comparable content of COX-1 protein in arterioles of WT and eNOS-KO mice. COX-2 protein, which was not detectable in arterioles of WT mice, was strongly expressed in arterioles of eNOS-KO mice, together with an upregulation of COX-2 gene expression. Immunohistochemical staining confirmed the presence of COX-2 in the endothelium of eNOS-KO arterioles. In conclusion, COX-2-derived PGs are the mediators responsible for maintenance of FID in arterioles of eNOS-deficient mice.
  • 13.

    【2hr】Lifetimes of Epicardial Rotors in Panoramic Optical Maps of Fibrillating Swine Ventricles

    包量

    机译 心房颤动的猪心室全景光学图中心外膜转子的寿命。
    摘要：During ventricular fibrillation (VF), electrical activation waves are fragmented and the heart cannot contract in synchrony. It has been proposed that VF waves emanate from stable periodic sources (often called “mother rotors”). The objective of the present study was to determine if stable rotors are consistently present on the epicardial surface of hearts comparable in size to human hearts. Using new optical mapping technology, we imaged VF from nearly the entire ventricular surface of 6 isolated swine hearts. Using newly developed pattern analysis algorithms, we identified and tracked VF wavefronts and phase singularities (PS: the pivot point of a reentrant wavefront). We introduce the notion of a compound rotor in which the rotor's central PS can change and describe an algorithm for automatically identifying such patterns. This prevents rotor lifetimes from being inappropriately abbreviated by wavefront fragmentation and collision events near the PS. We found that stable epicardial rotors were not consistently present during VF: only 1 of 17 VF episodes contained a compound rotor that lasted for the entire mapped interval of 4 s. However, shorter-lived rotors were common; 12.2±3.3 compound rotors with lifetime >200 ms were visible on the epicardium at any given instant. We conclude that epicardial mother rotors do not drive VF in this experimental model; if mother rotors do exist, they are intramural or septal. This paucity of persistent rotors suggests that individual rotors will eventually terminate by themselves and therefore that the continual formation of new rotors is critical for VF maintenance.
  • 14.

    【2hr】JNK Activation Decreases PP2A Regulatory Subunit, B56α, Expression and mRNA Stability and Increases AUF1 Expression in Cardiomyocytes

    包量

    机译 JNK激活减少心肌细胞中PP2A调节亚基，B56α，表达和mRNA稳定性并增加AUF1表达
    摘要：A central feature of heart disease is a molecular remodeling of signaling pathways in cardiac myocytes. This study focused on novel molecular elements of MAP kinase-mediated alterations in the pattern of gene expression of the protein phosphatase, PP2A. In an established model of sustained JNK activation a 70% decrease in expression of the targeting subunit of PP2A, B56α, was observed in either neonatal or adult cardiomyocytes. This loss in protein abundance was accompanied by a decrease of 69% in B56α mRNA steady-state levels. Given that the 3′-untranslated region of this transcript contains AU-rich elements known to regulate mRNA degradation, experiments explored the notion that instability of B56α mRNA accounts for the response. mRNA time course analyses with real time PCR methods showed that B56α transcript was transformed from a stable (no significant decay over 1 hr) to a labile form that rapidly degraded within minutes. These results were supported by complementary experiments that revealed that the RNA-binding protein AUF1, known to destabilize target mRNA, was increased 4-fold in JNK-activated cells. A variety of other stress-related stimuli, such as p38 MAP kinase activation and phorbol ester, upregulated AUF1 expression in cultured cardiac cells as well. In addition, gel mobility shift assays demonstrated that p37AUF1 binds with nanomolar affinity to segments of the B56α 3′-untranslated region. Thus, these studies provide new evidence that signaling-induced mRNA instability is an important mechanism that underlies the changes in the pattern of gene expression evoked by stress-activated pathways in cardiac cells.
  • 15.

    【2hr】Influence of Gender and Active Muscle Mass on Renal Vascular Responses During Static Exercise

    包量

    机译 性别和活跃的肌肉质量对静态运动过程中肾脏血管反应的影响
    摘要：During exercise, reflex renal vasoconstriction helps to maintain blood pressure and redistributes blood flow to the contracting muscle. Prior work has shown that gender and muscle mass can influence certain cardiovascular responses to exercise. Whether gender and/or muscle mass influence renal vasoconstrictor responses to exercise is unknown. We studied age and body mass index (BMI) matched healthy men (n = 10) and women (n = 10) during handgrip (HG, small muscle mass) and quadriceps contraction (QC, large muscle mass) as beat-to-beat changes in renal blood flow velocity (RBV; Duplex Ultrasound), mean arterial pressure (MAP; Finapres) and heart rate (ECG) were monitored. Renal vascular resistance index (RVR) was calculated by dividing MAP by RBV. Responses to HG vs. QC were compared in 13 subjects. We found that: 1) RVR responses to short bouts (15 sec) and fatiguing HG were similar in men and women (% change in RVR during 15 sec HG at 70% maximum voluntary contraction [MVC], male 23 ± 4% vs. female 31 ± 4%, P = NS); 2) post-handgrip circulatory responses were also similar in men and women; and 3) HG and QC were similar during short bouts (15 sec; % change in RVR during HG at 50% MVC, arm 19 ± 3% vs. leg 18 ± 5%, P = NS). Our findings suggest that muscle reflex mediated renal vasoconstriction is similar in men and women during static exercise. Moreover, muscle mass does not contribute to the magnitude of the reflex renal vasoconstrictor response seen with muscle contraction.
  • 16.

    【2hr】Genetic ablation of caveolin-1 modifies Ca2+ spark coupling in murine arterial smooth muscle cells

    包量

    机译 Caveolin-1的遗传消融修饰Ca2 +火花 鼠动脉平滑肌细胞中的偶联
    摘要：L-type, voltage-dependent calcium (Ca2+) channels, ryanodine-sensitive Ca2+ release (RyR) channels, and large-conductance Ca2+-activated potassium (KCa) channels comprise a functional unit that regulates smooth muscle contractility. Here, we investigated whether genetic ablation of caveolin-1 (cav-1), a caveolae protein, alters Ca2+ spark to KCa channel coupling and Ca2+ spark regulation by voltage-dependent Ca2+ channels in murine cerebral artery smooth muscle cells. Caveolae were abundant in the sarcolemma of control (cav-+/+) cells but were not observed in cav-1-deficient (cav-1−/−) cells. Ca2+ spark and transient KCa current frequency were approximately twofold higher in cav-1−/− than in cav-1+/+ cells. Although voltage-dependent Ca2+ current density was similar in cav-1+/+ and cav-1−/− cells, diltiazem and Cd2+, voltage-dependent Ca2+ channel blockers, reduced transient KCa current frequency to ∼55% of control in cav-1+/+ cells but did not alter transient KCa current frequency in cav-1−/− cells. Furthermore, although KCa channel density was elevated in cav-1−/− cells, transient KCa current amplitude was similar to that in cav-1+/+ cells. Higher Ca2+ spark frequency in cav-1−/− cells was not due to elevated intracellular Ca2+ concentration, sarcoplasmic reticulum Ca2+ load, or nitric oxide synthase activity. Similarly, Ca2+ spark amplitude and spread, the percentage of Ca2+ sparks that activated a transient KCa current, the amplitude relationship between sparks and transient KCa currents, and KCa channel conductance and apparent Ca2+ sensitivity were similar in cav-1+/+ and cav-1−/− cells. In summary, cav-1 ablation elevates Ca2+ spark and transient KCa current frequency, attenuates the coupling relationship between voltage-dependent Ca2+ channels and RyR channels that generate Ca2+ sparks, and elevates KCa channel density but does not alter transient KCa current activation by Ca2+ sparks. These findings indicate that cav-1 is required for physiological Ca2+ spark and transient KCa current regulation in cerebral artery smooth muscle cells.
  • 17.

    【2hr】Exercise training improves femoral artery blood flow responses to endothelium-dependent dilators in hypercholesterolemic pigs

    包量

    机译 运动训练可改善高胆固醇血症猪对内皮依赖性扩张剂的股动脉血流反应
    摘要：We tested two hypotheses: 1) that the effects of hypercholesterolemia on endothelial function in femoral arteries exceed those reported in brachial arteries and 2) that exercise (Ex) training enhances endothelium-dependent dilation and improves femoral artery blood flow (FABF) in hypercholesterolemic pigs. Adult male pigs were fed a normal fat (NF) or high-fat/cholesterol (HF) diet for 20 wk. Four weeks after the diet was initiated, pigs were Ex trained or remained sedentary (Sed) for 16 wk, thus yielding four groups: NF-Sed, NF-Ex, HF-Sed, and HF-Ex. Endothelium-dependent vasodilator responses were assessed in vivo by measuring changes in FABF after intra-arterial injections of ADP and bradykinin (BK). Endothelium-dependent and -independent relaxation was assessed in vitro by measuring relaxation responses to BK and sodium nitroprusside (SNP). FABF increased in response to ADP and BK in all groups. FABF responses to ADP and BK were not impaired by HF but were improved by Ex in HF pigs. BK- and SNP-induced relaxation of femoral artery rings was not altered by HF or Ex. To determine whether the mechanism(s) for vasorelaxation of femoral arteries was altered by HF or Ex, BK-induced relaxation was assessed in vitro in the absence or presence of NG-nitro-L-arginine methyl ester [L-NAME; to inhibit nitric oxide synthase (NOS)], indomethacin (Indo; to inhibit cyclooxygenase), or L-NAME + Indo. BK-induced relaxation was inhibited by L-NAME and L-NAME + Indo in all groups of femoral arteries. Ex increased the NOS-dependent component of endothelium-dependent relaxation in NF (not HF) arteries. Indo did not inhibit BK-induced relaxation. Collectively, these results indicate that hypercholesterolemia does not alter endothelial function in femoral arteries and that Ex training improves FABF responses to ADP and BK; however, the improvement cannot be attributed to enhanced endothelial function in HF femoral arteries. These data suggest that Ex-induced improvements in FABF in HF arteries are mediated by vascular adaptations in arteries/arterioles downstream from the femoral artery.
  • 18.

    【2hr】Isolation and characterization of coronary endothelial and smooth muscle cells from A1 adenosine receptor-knockout mice

    包量

    机译 A1腺苷受体敲除小鼠的冠状动脉内皮和平滑肌细胞的分离与鉴定
    摘要：Mice have been used widely in in vivo and in vitro cardiovascular research. The availability of knockout mice provides further clues to the physiological significance of specific receptor subtypes. Adenosine A1 receptor (A1AR)-knockout (A1KO) mice and their wild-type (A1WT) controls were employed in this investigation. The heart and aortic arch were carefully removed and retroinfused with enzyme solution (1 mg/ml collagenase type I, 0.5 mg/ml soybean trypsin inhibitor, 3% BSA, and 2% antibiotics) through the aortic arch. The efflux was collected at 30-, 60-, and 90-min intervals. The cells were centrifuged, and the pellets were mixed with medium [medium 199-F-12 medium with 10% FBS and 2% antibiotics (for endothelial cells) and advanced DMEM with 10% FBS, 10% mouse serum, 2% GlutaMax, and 2% antibiotics (for smooth muscle cells)] and plated. Endothelial cells were characterized by a cobblestone appearance and positive staining with acetylated LDL labeled with 1,1′-dioctadecyl-3,3,3′,3-tetramethylindocarbocyanine perchlorate. Smooth muscle cells were characterized by positive staining of smooth muscle α-actin and smooth muscle myosin heavy chain. Homogeneity of the smooth muscle cells was ~91%. Western blot analysis showed expression of smoothelin in the cells from passages 3, 7, and 11 in A1WT and A1KO mice. Furthermore, the A1AR was characterized by Western blot analysis using an A1AR-specific antibody. To our knowledge, this is the first isolation and successful characterization of smooth muscle cells from the mouse coronary system.
  • 19.

    【2hr】Hypertonic saline dextran after burn injury decreases inflammatory cytokine responses to subsequent pneumonia-related sepsis

    包量

    机译 烧伤后高渗盐水右旋糖酐降低对随后的肺炎相关败血症的炎性细胞因子反应
    摘要：The present study examined the hypothesis that hypertonic saline dextran (HSD), given after an initial insult, attenuates exaggerated inflammation that occurs with a second insult. Adult rats (n = 15 per group) were divided into groups 1 (sham burn), 2 [40% total body surface area burn + 4 ml/kg isotonic saline (IS) + 4 ml·kg−1 ·% burn−1 lactated Ringer solution (LR)], and 3 (burn + 4 ml/kg HSD + LR), all studied 24 h after burns. Groups 4 (sham burn), 5 (burn + IS + LR), and 6 (burns + HSD + LR) received intratracheal (IT) vehicle 7 days after burns; groups 7 (burn + IS + LR) and 8 (burn + HSD + LR) received IT Streptococcus pneumoniae (4 × 106 colony-forming units) 7 days after burn. Groups 4–8 were studied 8 days after burn and 24 h after IT septic challenge. When compared with sham burn, contractile defects occurred 24 h after burn in IS-treated but not HSD-treated burns. Cardiac inflammatory responses (pg/ml TNF-α) were evident with IS (170 ± 10) but not HSD (45 ± 5) treatment vs. sham treatment (80 ± 15). Pneumonia-related sepsis 8 days after IS-treated burns (group 7) exacerbated TNF-α responses/contractile dysfunction vs. IS-treated burns in the absence of sepsis (P < 0.05). Sepsis that occurred after HSD-treated burns (group 8) had less myocyte TNF-α secretion/better contractile function than IS-treated burns given septic challenge (group 7, P < 0.05). We conclude that an initial burn injury exacerbates myocardial inflammation/dysfunction occurring with a second insult; giving HSD after the initial insult attenuates myocardial inflammation/dysfunction associated with a second hit, suggesting that HSD reduces postinjury risk for infectious complications.
  • 20.

    【2hr】Kallikrein activates bradykinin B2 receptors in the absence of kininogen

    包量

    机译 激肽原不存在时激肽释放酶激活缓激肽B2受体
    摘要：Kallikreins cleave plasma kininogens to release the bioactive peptides bradykinin (BK) or kallidin (Lys-BK). These peptides then activate widely disseminated B2 receptors with consequences that may be either noxious or beneficial. We used cultured cells to show that kallikrein can bypass kinin release to activate BK B2 receptors directly. To exclude intermediate kinin release or kininogen uptake from the culture medium, we cultured and maintained cells in medium entirely free of animal proteins. We compared the responses of stably transfected CHO cells that express human B2 receptors (CHO-B2) and cells that co-express angiotensin I-converting enzyme (ACE) as well (CHO AB). We found that BK (1 nM or more) and tissue kallikrein (1–10 nM) both significantly increased release of arachidonic acid beyond unstimulated or baseline levels. An enzyme-linked immunoassay for kinin established that kallikrein did not release a kinin from CHO cells. We confirmed the absence of kininogen mRNA with RT-PCR to rule out kininogen synthesis by CHO cells. Next, we tested an ACE inhibitor for enhanced BK receptor activation in the absence of kinin release and synthesized an ACE-resistant BK analogue as a control for these experiments. Enalaprilat (1μM) potentiated kallikrein (100 nM) in CHO AB cells but was ineffective in CHO B2 cells that do not bear ACE. We concluded that kallikrein activated B2 receptors without releasing a kinin. Furthermore, inhibition of ACE enhanced the receptor activation by kallikrein, an action that may contribute to the manifold therapeutic effects of ACE inhibitors.
题名 作者 来源 发表时间

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号