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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

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  • 刊频： Twice monthly, Feb. 2012-
  • NLM标题： Am J Physiol Heart Circ Physiol
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  • 1.

    【2hr】Mining Natural Products for Cardiovascular Benefits: Nitrosative stress uncovers potent β2-adrenergic receptor-linked vasodilation further enhanced by blockade of clathrin endosome formation

    包量

    机译 开采具有心血管益处的天然产物：亚硝酸盐胁迫揭示了有效的β2-肾上腺素能受体相关的血管舒张作用其通过阻断网格蛋白内体形成而进一步增强
    摘要：This study investigated the effect of sodium nitroprusside (SNP) preexposure on vasodilation via the β-adrenergic receptor (BAR) system. SNP was used as a nitrosative/oxidative proinflammatory insult. Small arterioles were visualized by intravital microscopy in the hamster cheek pouch tissue (isoflurane, n = 45). Control dilation to isoproterenol (EC50: 10−7 mol/l) became biphasic as a function of concentration after 2 min of exposure to SNP (10−4 M), with increased potency at picomolar dilation uncovered and decreased efficacy at the micromolar dilation. Control dilation to curcumin was likewise altered after SNP, but only the increased potency at a low dose was uncovered, whereas micromolar dilation was eliminated. The picomolar dilations were blocked by the potent BAR-2 inverse agonist carazolol (10−9 mol/l). Dynamin inhibition with dynasore mimicked this effect, suggesting that SNP preexposure prevented BAR agonist internalization. Using HeLa cells transfected with BAR-2 tagged with monomeric red fluorescent protein, exposure to 10−8−10−6 mol/l curcumin resulted in internalization and colocalization of BAR-2 and curcumin (FRET) that was prevented by oxidative stress (10−3 mol/l CoCl2), supporting that stress prevented internalization of the BAR agonist with the micromolar agonist. This study presents novel data supporting that distinct pools of BARs are differentially available after inflammatory insult.>NEW & NOTEWORTHY Preexposure to an oxidativeitrosative proinflammatory insult provides a “protective preconditioning” against future oxidative damage. We examined immediate vasoactive and molecular consequences of a brief preexposure via β-adrenergic receptor signaling in small arterioles. Blocked receptor internalization with elevated reactive oxygen levels coincides with a significant and unexpected vasodilation to β-adrenergic agonists at picomolar doses.
  • 2.

    【2hr】Integrative Cardiovascular Physiology and Pathophysiology: Noninvasive assessment of the common carotid artery hemodynamics with increasing exercise work rate using wave intensity analysis

    包量

    机译 综合心血管生理学和病理生理学：使用波强度分析随着运动量的增加对颈总动脉血流动力学的无创评估
    摘要：Noninvasively determined local wave speed (c) and wave intensity (WI) parameters provide insights into arterial stiffness and cardiac-vascular interactions in response to physiological perturbations. However, the effects of incremental exercise and subsequent recovery on c and WI have not been fully established. We examined the changes in c and WI parameters in the common carotid artery (CCA) during exercise and recovery in eight young, healthy male athletes. Ultrasound measurements of CCA diameter and blood flow velocity were acquired at rest, during five stages of incremental exercise (up to 70% maximum work rate), and throughout 1 h of recovery, and noninvasive WI analysis [diameter-velocity (DU) approach] was performed. During exercise, c increased (+136%), showing increased stiffness with work rate. All peak and area of forward compression, backward compression, and forward expansion waves increased during exercise (+452%, +700%, and +900%, respectively). However, WI reflection indexes and CCA resistance did not significantly change from rest to exercise. Furthermore, wave speed and the magnitude of all waves returned to baseline within 5 min of recovery, suggesting that the effects of exercise in the investigated parameters of young, healthy individuals were transient. In conclusion, incremental exercise was associated with an increase in local CCA stiffness and increases in all wave parameters, indicative of enhanced ventricular contractility and improved late-systolic blood flow deceleration.>NEW & NOTEWORTHY We examined hemodynamics of the common carotid artery using noninvasive application of wave intensity analysis during exercise and recovery. The hemodynamic adjustments to exercise were associated with increases in local common carotid artery stiffness and all waves’ parameters, with the latter indicating enhanced ventricular contractility and improved late systolic blood flow deceleration.
  • 3.

    【2hr】Extracellular Matrix in Cardiovascular Pathophysiology: Impact of chronic hypoxia on proximal pulmonary artery wave propagation and mechanical properties in rats

    包量

    机译 心血管病理生理学中的细胞外基质：慢性低氧对大鼠近端肺动脉波传播和力学特性的影响
    摘要：Arterial stiffness and wave reflection are important components of the ventricular afterload. Therefore, we aimed to assess the arterial wave characteristics and mechanical properties of the proximal pulmonary arteries (PAs) in the hypoxic pulmonary hypertensive rat model. After 21 days in normoxic or hypoxic chambers (24 animals/group), animals underwent transthoracic echocardiography and PA catheterization with a dual-tipped pressure and Doppler flow sensor wire. Wave intensity analysis was performed. Artery rings obtained from the pulmonary trunk, right and left PAs, and aorta were subjected to a tensile test to rupture. Collagen and elastin content were determined. In hypoxic rats, proximal PA wall thickness, collagen content, tensile strength per unit collagen, maximal elastic modulus, and wall viscosity increased, whereas the elastin-to-collagen ratio and arterial distensibility decreased. Arterial pulse wave velocity was also increased, and the increase was more prominent in vivo than ex vivo. Wave intensity was similar in hypoxic and normoxic animals with negligible wave reflection. In contrast, the aortic maximal elastic modulus remained unchanged, whereas wall viscosity decreased. In conclusion, there was no evidence of altered arterial wave propagation in proximal PAs of hypoxic rats while the extracellular matrix protein composition was altered and collagen tensile strength increased. This was accompanied by altered mechanical properties in vivo and ex vivo.>NEW & NOTEWORTHY In rats exposed to chronic hypoxia, we have shown that pulse wave velocity in the proximal pulmonary arteries increased and pressure dependence of the pulse wave velocity was steeper in vivo than ex vivo leading to a more prominent increase in vivo.
  • 4.

    【2hr】Translational Physiology: Hypothesis: role for ammonia neutralization in the prevention and reversal of heart failure

    包量

    机译 转化生理学：假设：氨中和在预防和逆转心力衰竭中的作用
    • 作者：Oscar H. L. Bing
    • 刊名：American Journal of Physiology - Heart and Circulatory Physiology
    • -1年第5期
    摘要：Ammonia plays a central role in the life and death of all living organisms and has been studied for over 100 yr. Ammonia is necessary for growth and development, but it is toxic in excess, and, as a result, differing methods of ammonia neutralization have evolved. After physiological and pathological stress to the heart, tissue ammonia levels rise. Local ammonia neutralization may be inadequate, and excess ammonia may exert its toxic effects. Phenylbutyrate (PBA), which is Federal Drug Administration approved for the treatment of elevated blood ammonia in urea cycle disorders, provides an accessory pathway for ammonia excretion. Recently, PBA has also been found to prevent specific cardiomyopathies. The central theme presents the hypothesis that stress to the myocardium from a variety of environmental sources causes injury, cell death, necrosis, and ammonia production. Ammonia, if not neutralized, exerts downstream toxic effects. Here, data are presented showing that neutralization with PBA alone and PBA combined with angiotensin-converting enzyme inhibition prevent and reverse pathophysiology associated with specific cardiomyopathies.>NEW & NOTEWORTHY Ammonia produced after myocardial injury is hypothesized to be an upstream stress contributing to the pathophysiology of heart failure, effects that may be attenuated by a documented ammonia-reducing treatment. Reversal of heart failure can be achieved using an angiotensin-converting enzyme inhibitor combined with an ammonia-reducing treatment.
  • 5.

    【2hr】Integrative Cardiovascular Physiology and Pathophysiology: Eight weeks of nitrate supplementation improves blood flow and reduces the exaggerated pressor response during forearm exercise in peripheral artery disease

    包量

    机译 综合心血管生理学和病理生理学：补充硝酸盐八周可改善周围动脉疾病前臂运动过程中的血流量并减少过度的升压反应
    摘要：Peripheral artery disease (PAD) is characterized by a reduced blood flow (BF) and an elevated blood pressure (pressor) response during lower extremity exercise. Although PAD is evident in the upper extremities, no studies have determined BF and pressor responses during upper extremity exercise in PAD. Emerging evidence suggests that inorganic nitrate supplementation may serve as an alternative dietary strategy to boost nitric oxide bioavailability, improving exercising BF and pressor responses during exercise. The present study investigated 1) BF and pressor responses to forearm exercise in patients with PAD (n = 21) relative to healthy age-matched control subjects (n = 16) and 2) whether 8 wk of NaNO3 supplementation influenced BF and pressor responses to forearm exercise in patients with PAD. Patients with moderate to severe PAD were randomly assigned to a NaNO3 (1 g/day, n = 13)-treated group or a placebo (microcrystalline cellulose, n = 8)-treated group. Brachial artery forearm BF (FBF; via Doppler) and blood pressure (via finger plethysmography) were measured during mild-intensity (~3.5-kg) and moderate-intensity (~7-kg) handgrip exercise. The absolute change (from baseline) in FBF was reduced (except in the 3.5-kg condition) and BP responses were increased in patients with PAD compared with healthy control subjects in 3.5- and 7-kg conditions (all P < 0.05). Plasma nitrate and nitrite were elevated, exercising (7-kg) ΔFBF was improved (from 141 ± 17 to 172 ± 20 ml/min), and mean arterial pressure response was reduced (from 13 ± 1 to 9 ± 1 mmHg, P < 0.05) in patients with PAD that received NaNO3 supplementation for 8 wk relative to those that received placebo. These results suggest that the BF limitation and exaggerated pressor response to moderate-intensity forearm exercise in patients with PAD are improved with 8 wk of NaNO3 supplementation.>NEW & NOTEWORTHY Peripheral artery disease (PAD) results in an exaggerated pressor response and reduced blood flow during lower limb exercise; however, the effect of PAD in the upper limbs has remained unknown. These results suggest that 8 wk of inorganic nitrate supplementation improves the blood flow limitation and exaggerated pressor response to moderate-intensity forearm exercise in PAD.
  • 6.

    【2hr】Integrative Cardiovascular Physiology and Pathophysiology: UBC-Nepal Expedition: imposed oscillatory shear stress does not further attenuate flow-mediated dilation during acute and sustained hypoxia

    包量

    机译 综合心血管生理学和病理生理学：UBC-尼泊尔远征：在急性和持续性缺氧期间施加的振荡切应力不能进一步减弱血流介导的扩张
    摘要：Experimentally induced oscillatory shear stress (OSS) and hypoxia reduce endothelial function in humans. Acute and sustained hypoxia may cause increases in resting OSS; however, whether this influences endothelial susceptibility to further increases in OSS is unknown. Healthy lowlanders (n = 15, 30 ± 6 yr; means ± SD) participated in three OSS interventions: two interventions at sea level [normoxia and after 20 min of normobaric hypoxia (acute hypoxia, 11% O2)] and one intervention 5–7 days after a 9-day ascent to 5,050 m (sustained hypoxia). OSS was provoked in the brachial artery using a 30-min distal cuff inflation (75 mmHg). Endothelial function was assessed before and after each intervention by reactive hyperemia flow-mediated dilation (FMD). Shear stress magnitude and patterns were obtained via Duplex ultrasound. Baseline retrograde shear stress and OSS were greater in acute hypoxia versus normoxia (P < 0.001), and OSS was elevated in sustained hypoxia versus normoxia (P = 0.011). The intervention further augmented OSS during each condition. Preintervention FMD was decreased by 29 ± 48% in acute hypoxia and by 25 ± 31% in sustained hypoxia compared with normoxia (P = 0.001 and 0.026); these changes correlated with changes in baseline mean and antegrade shear stress. After the intervention, FMD decreased during normoxia (−41 ± 26%, P < 0.001) and was unaltered during acute or sustained hypoxia. Therefore, a 30-min exposure to OSS reduced FMD during normoxia, a condition with an unchallenged, healthy endothelium; however, imposed OSS did not appear to worsen endothelial function during acute or sustained hypoxia. Exposure to an altered magnitude and pattern of shear stress at baseline in hypoxia may contribute to the insensitivity to further acute augmentation of OSS.>NEW & NOTEWORTHY We investigated whether the endothelium remains sensitive to experimental increases in oscillatory shear stress in acute (11% O2) and sustained (2 wk at 5,050 m) hypoxia. Hypoxia altered baseline shear stress and decreased endothelial function (flow-mediated dilation); however, exposure to experimentally induced oscillatory shear stress only impaired flow-mediated dilation in normoxia.
  • 7.

    【2hr】Galectin-3 in the pathogenesis of heart failure: a causative mediator or simply a biomarker?

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    机译 Galectin-3在心力衰竭的发病机理中：是致病性介质还是仅仅是生物标志物？
    摘要：
  • 8.

    【2hr】Vascular Biology and Microcirculation: Effects of teriparatide on morphology of aortic calcification in aged hyperlipidemic mice

    包量

    机译 血管生物学和微循环：特立帕肽对老年高脂血症小鼠主动脉钙化形态的影响
    摘要：Calcific aortic vasculopathy correlates with bone loss in osteoporosis in an age-independent manner. Prior work suggests that teriparatide, the bone anabolic treatment for postmenopausal osteoporosis, may inhibit the onset of aortic calcification. Whether teriparatide affects the progression of preexisting aortic calcification, widespread among this patient population, is unknown. Female apolipoprotein E-deficient mice were aged for over 1 yr to induce aortic calcification, treated for 4.5 wk with daily injections of control vehicle (PBS), 40 µg/kg teriparatide (PTH40), or 400 µg/kg teriparatide (PTH400), and assayed for aortic calcification by microcomputed tomography (microCT) before and after treatment. In a followup cohort, aged female apolipoprotein E-deficient mice were treated with PBS or PTH400 and assayed for aortic calcification by serial microCT and micropositron emission tomography. In both cohorts, aortic calcification detected by microCT progressed similarly in all groups. Mean aortic 18F-NaF incorporation, detected by serial micropositron emission tomography, increased in the PBS-treated group (+14 ± 5%). In contrast, 18F-NaF incorporation decreased in the PTH400-treated group (−33 ± 20%, P = 0.03). Quantitative histochemical analysis by Alizarin red staining revealed a lower mineral surface area index in the PTH400-treated group compared with the PBS-treated group (P = 0.04). Furthermore, Masson trichrome staining showed a significant increase in collagen deposition in the left ventricular myocardium of mice that received PTH400 [2.1 ± 0.6% vs. control mice (0.5 ± 0.1%), P = 0.02]. In summary, although teriparatide may not affect the calcium mineral content of aortic calcification, it reduces 18F-NaF uptake in calcified lesions, suggesting the possibility that it may reduce mineral surface area with potential impact on plaque stability.>NEW & NOTEWORTHY Parathyroid hormone regulates bone mineralization and may also affect vascular calcification, which is an important issue, given that its active fragment, teriparatide, is widely used for the treatment of osteoporosis. To determine whether teriparatide alters vascular calcification, we imaged aortic calcification in mice treated with teriparatide and control mice. Although teriparatide did not affect the calcium content of cardiovascular deposits, it reduced their fluoride tracer uptake.
  • 9.

    【2hr】Cardiovascular Aging: New Frontiers and Old Friends: Impact of pulse pressure on cerebrovascular events leading to age-related cognitive decline

    包量

    机译 心血管衰老：新领域和老朋友：脉压对导致年龄相关性认知下降的脑血管事件的影响
    摘要：Aging is a modern concept: human life expectancy has more than doubled in less than 150 yr in Western countries. Longer life span, however, reveals age-related diseases, including cerebrovascular diseases. The vascular system is a prime target of aging: the “wear and tear” of large elastic arteries exposed to a lifelong pulsatile pressure causes arterial stiffening by fragmentation of elastin fibers and replacement by stiffer collagen. This arterial stiffening increases in return the amplitude of the pulse pressure (PP), its wave penetrating deeper into the microcirculation of low-resistance, high-flow organs such as the brain. Several studies have associated peripheral arterial stiffness responsible for the sustained increase in PP, with brain microvascular diseases such as cerebral small vessel disease, cortical gray matter thinning, white matter atrophy, and cognitive dysfunction in older individuals and prematurely in hypertensive and diabetic patients. The rarefaction of white matter is also associated with middle cerebral artery pulsatility that is strongly dependent on PP and artery stiffness. PP and brain damage are likely associated, but the sequence of mechanistic events has not been established. Elevated PP promotes endothelial dysfunction that may slowly develop in parallel with the accumulation of proinflammatory senescent cells and oxidative stress, generating cerebrovascular damage and remodeling, as well as brain structural changes. Here, we review data suggesting that age-related increased peripheral artery stiffness may promote the penetration of a high PP to cerebral microvessels, likely causing functional, structural, metabolic, and hemodynamic alterations that could ultimately promote neuronal dysfunction and cognitive decline.
  • 10.

    【2hr】Integrative Cardiovascular Physiology and Pathophysiology: Protection from chronic stress- and depressive symptom-induced vascular endothelial dysfunction in female rats is abolished by preexisting metabolic disease

    包量

    机译 综合心血管生理学和病理生理学：预先存在的代谢性疾病废除了保护雌性大鼠免受慢性应激和抑郁症状引起的血管内皮功能障碍的保护
    摘要：While it is known that chronic stress and clinical depression are powerful predictors of poor cardiovascular outcomes, recent clinical evidence has identified correlations between the development of metabolic disease and depressive symptoms, creating a combined condition of severely elevated cardiovascular disease risk. In this study, we used the obese Zucker rat (OZRs) and the unpredictable chronic mild stress (UCMS) model to determine the impact of preexisting metabolic disease on the relationship between chronic stress/depressive symptoms and vascular function. Additionally, we determined the impact of metabolic syndrome on sex-based protection from chronic stress/depressive effects on vascular function in female lean Zucker rats (LZRs). In general, vasodilator reactivity was attenuated under control conditions in OZRs compared with LZRs. Although still impaired, conduit arterial and resistance arteriolar dilator reactivity under control conditions in female OZRs was superior to that in male or ovariectomized (OVX) female OZRs, largely because of better maintenance of vascular nitric oxide and prostacyclin levels. However, imposition of metabolic syndrome in combination with UCMS in OZRs further impaired dilator reactivity in both vessel subtypes to a similarly severe extent and abolished any protective effect in female rats compared with male or OVX female rats. The loss of vascular protection in female OZRs with UCMS was reflected in vasodilator metabolite levels, which closely matched those in male and OVX female OZRs subjected to UCMS. These results suggest that presentation of metabolic disease in combination with depressive symptoms can overwhelm the vasoprotection identified in female rats and, thereby, may reflect a severe impairment to normal endothelial function.>NEW & NOTEWORTHY This study addresses the protection from chronic stress- and depression-induced vascular dysfunction identified in female compared with male or ovariectomized female rats. We determined the impact of preexisting metabolic disease, a frequent comorbidity of clinical depression in humans, on that vascular protection. With preexisting metabolic syndrome, female rats lost all protection from chronic stress/depressive symptoms and became phenotypically similar to male and ovariectomized female rats, with comparably poor vasoactive dilator metabolite profiles.
  • 11.

    【2hr】Vascular Biology and Microcirculation: Water transport and homeostasis as a major function of erythrocytes

    包量

    机译 血管生物学和微循环：输水和体内平衡是红细胞的主要功能
    摘要：Erythrocytes have long been known to change volumes and shapes in response to different salt concentrations. Aquaporin-1 (AQP1) was discovered in their membranes more than 20 yr ago. The physiological roles of volume changes and AQP1 expression, however, have remained unclear. We propose that rapid water exchange through AQP1 coupled with large capacity for volume change may allow erythrocytes to play an important role in water regulation. In this study, we showed that erythrocytes in situ gradually reduced their volumes by 39% in response to the hyperosmotic corticomedullary gradient within mouse kidneys. AQP1 knockout (KO) erythrocytes, however, displayed only minimal reduction. Constructing a microfluidic device resembling capillary flow with an extracellular fluorescent reporter demonstrated that water exchanges between erythrocytes and their hypotonic or hypertonic surroundings in vitro reached steady state in ~60 ms. AQP1 KO erythrocytes, however, did not show significant change. To simulate the water transport in circulation, we built basic units consisting of three compartments (i.e., erythrocyte, plasma, and interstitial fluid) using Kedem-Katchalsky equations for membrane transport, and connected multiple units to account for the blood flow. These simulations agreed with experimental results. Importantly, volume-changing erythrocytes in capillaries always “increase” the osmotic gradient between plasma and interstitial fluid, making them function as “micropumps” to speed up the regulation of local osmolarity. Trillions of these micropumps, mobile throughout the body, may further contribute to water homeostasis. These insights suggest that the enhanced exchange of water, in addition to O2 and CO2, may well be the third major function of erythrocytes.>NEW & NOTEWORTHY Physiological roles of erythrocyte volume change and aquaporin-1 were proposed and investigated here. We conclude that fast water transport by aquaporin-1 coupled with large volume-change capacity allows erythrocytes to enhance water exchange with local tissues. Furthermore, their huge number and mobility allow them to contribute to body water homeostasis.
  • 12.

    【2hr】Signaling and Stress Response: Myocardial infarction-induced microRNA-enriched exosomes contribute to cardiac Nrf2 dysregulation in chronic heart failure

    包量

    机译 信号传导和应激反应：心肌梗塞诱导的富含microRNA的外泌体在慢性心力衰竭中导致心脏Nrf2失调
    摘要：The imbalance between the synthesis of reactive oxygen species and their elimination by antioxidant defense systems results in macromolecular damage and disruption of cellular redox signaling, affecting cardiac structure and function, thus contributing to contractile dysfunction, myocardial hypertrophy, and fibrosis in chronic heart failure [chronic heart failure (CHF)]. The Kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is an important antioxidant defense mechanism and is closely associated with oxidative stress-mediated cardiac remodeling in CHF. In the present study, we investigated the regulation of myocardial Nrf2 in the postmyocardial infarction (post-MI) state. Six weeks post-MI, Nrf2 protein was downregulated in the heart, resulting in a decrease of Nrf2-targeted antioxidant enzymes, whereas paradoxically the transcription of Nrf2 was increased, suggesting that translational inhibition of Nrf2 may contribute to the dysregulation in CHF. We therefore hypothesized that microRNAs may be involved in the translational repression of Nrf2 mRNA in the setting of CHF. Using quantitative real-time PCR analysis, we found that three microRNAs, including microRNA-27a, microRNA-28-3p, and microRNA-34a, were highly expressed in the left ventricle of infarcted hearts compared with other organs. Furthermore, in vitro analysis revealed that cultured cardiac myocytes and fibroblasts expressed these three microRNAs in response to TNF-α stimulation. These microRNAs were preferentially incorporated into exosomes and secreted into the extracellular space in which microRNA-enriched exosomes mediated intercellular communication and Nrf2 dysregulation. Taken together, these results suggest that increased local microRNAs induced by MI may contribute to oxidative stress by the inhibition of Nrf2 translation in CHF.>NEW & NOTEWORTHY The results of this work provide a novel mechanism mediated by microRNA-enriched exosomes, contributing to the nuclear factor erythroid 2-related factor 2 dysregulation and subsequent oxidative stress. Importantly, these new findings will provide a promising strategy to improve the therapeutic efficacy through targeting nuclear factor erythroid 2-related factor 2-related microRNAs in the chronic heart failure state, which show potentially clinical applications.
  • 13.

    【2hr】Vascular Biology and Microcirculation: Actin polymerization contributes to enhanced pulmonary vasoconstrictor reactivity after chronic hypoxia

    包量

    机译 血管生物学和微循环：慢性缺氧后肌动蛋白聚合有助于增强肺血管收缩反应性
    摘要：Chronic hypoxia (CH) augments basal and endothelin-1 (ET-1)-induced pulmonary vasoconstrictor reactivity through reactive oxygen species (ROS) generation and RhoA/Rho kinase (ROCK)-dependent myofilament Ca2+ sensitization. Because ROCK promotes actin polymerization and the actin cytoskeleton regulates smooth muscle tension, we hypothesized that actin polymerization is required for enhanced basal and ET-1-dependent vasoconstriction after CH. To test this hypothesis, both end points were monitored in pressurized, endothelium-disrupted pulmonary arteries (fourth-fifth order) from control and CH (4 wk at 0.5 atm) rats. The actin polymerization inhibitors cytochalasin and latrunculin attenuated both basal and ET-1-induced vasoconstriction only in CH vessels. To test whether CH directly alters the arterial actin profile, we measured filamentous actin (F-actin)-to-globular actin (G-actin) ratios by fluorescent labeling of F-actin and G-actin in fixed pulmonary arteries and actin sedimentation assays using homogenized pulmonary artery lysates. We observed no difference in actin polymerization between groups under baseline conditions, but ET-1 enhanced actin polymerization in pulmonary arteries from CH rats. This response was blunted by the ROS scavenger tiron, the ROCK inhibitor fasudil, and the mDia (RhoA effector) inhibitor small-molecule inhibitor of formin homology domain 2. Immunoblot analysis revealed an effect of CH to increase both phosphorylated (inactive) and total levels of the actin disassembly factor cofilin but not phosphorylated cofilin-to-total cofilin ratios. We conclude that actin polymerization contributes to increased basal pulmonary arterial constriction and ET-1-induced vasoconstrictor reactivity after CH in a ROS- and ROCK-dependent manner. Our results further suggest that enhanced ET-1-mediated actin polymerization after CH is dependent on mDia but independent of changes in the phosphorylated cofilin-to-total cofilin ratio.>NEW & NOTEWORTHY This research is the first to demonstrate a role for actin polymerization in chronic hypoxia-induced basal pulmonary arterial constriction and enhanced agonist-induced vasoconstrictor activity. These results suggest that a reactive oxygen species-Rho kinase-actin polymerization signaling pathway mediates this response and may provide a mechanistic basis for the vasoconstrictor component of pulmonary hypertension.
  • 14.

    【2hr】Integrative Cardiovascular Physiology and Pathophysiology: Sex differences in abdominal aortic aneurysms

    包量

    机译 综合心血管生理学和病理生理学：腹主动脉瘤的性别差异
    摘要：Abdominal aortic aneurysm (AAA) is a vascular disorder with a high case fatality rate in the instance of rupture. AAA is a multifactorial disease, and the etiology is still not fully understood. AAA is more likely to occur in men, but women have a greater risk of rupture and worse prognosis. Women are reportedly protected against AAA possibly by premenopausal levels of estrogen and are, on average, diagnosed at older ages than men. Here, we review the present body of research on AAA pathophysiology in humans, animal models, and cultured cells, with an emphasis on sex differences and sex steroid hormone signaling.
  • 15.

    【2hr】The Yin and Yang of endothelium-derived vasodilator factors

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    机译 内皮源性血管扩张因子的阴阳
    摘要：
  • 16.

    【2hr】Guidelines in Cardiovascular Research: Guidelines for authors and reviewers on antibody use in physiology studies

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    机译 心血管研究指南：生理研究中抗体使用的作者和审稿人指南
    摘要：Antibody use is a critical component of cardiovascular physiology research, and antibodies are used to monitor protein abundance (immunoblot analysis) and protein expression and localization (in tissue by immunohistochemistry and in cells by immunocytochemistry). With ongoing discussions on how to improve reproducibility and rigor, the goal of this review is to provide best practice guidelines regarding how to optimize antibody use for increased rigor and reproducibility in both immunoblot analysis and immunohistochemistry approaches.Listen to this article’s corresponding podcast at .
  • 17.

    【2hr】Vascular Biology and Microcirculation: Differences in L-type Ca2+ channel activity partially underlie the regional dichotomy in pumping behavior by murine peripheral and visceral lymphatic vessels

    包量

    机译 血管生物学和微循环：L型Ca2 +通道活性的差异部分是鼠外周和内脏淋巴管的抽动行为的区域二分法的基础
    摘要：We identified a regional dichotomy in murine lymphatic contractile function with regard to vessel location within the periphery or visceral cavity. All vessels isolated from peripheral regions [cervical, popliteal, inguinal, axillary, and internodal inguinal axillary (Ing-Ax)] developed robust contractions with maximal ejection fractions (EFs) of 50–80% in our ex vivo isobaric myograph experiments. Conversely, vessels isolated from the visceral cavity (mesenteric, thoracic duct, and iliac) demonstrated maximal EFs of ≤10%. Using pressure myography, sharp electrode membrane potential recordings, and Ca2+ imaging, we assessed the role of L-type Ca2+ channels in this contractile dichotomy. Ing-Ax membrane potential revealed a ~2-s action potential (AP) cycle (resting −35 mV, spike −5 mV, and plateau −11 mV) with a plateau phase that was significantly lengthened by the L-type Ca2+ channel agonist Bay K8644 (BayK; 100 nM). APs recorded from mesenteric vessels, however, displayed a slower upstroke and an elongated time over threshold. BayK (100 nM) increased the mesenteric AP upstroke velocity and plateau duration but also significantly hyperpolarized the vessel. Contractions of vessels from both regions were preceded by Ca2+ flashes, detected with a smooth muscle-specific endogenous Ca2+ reporter, that typically were coordinated over the length of the vessel. Similar to the membrane potential recordings, Ca2+ flashes in mesenteric vessels were weaker and had a slower rise time but were longer lasting than those in Ing-Ax vessels. BayK (100 nM) significantly increased the Ca2+ transient amplitude and duration in both vessels and decreased time to peak Ca2+ in mesenteric vessels. However, a higher concentration (1 μM) of BayK was required to produce even a modest increase in EF in visceral lymphatics, which remained at <20%.>NEW & NOTEWORTHY Lymphatic collecting vessels isolated from murine peripheral tissues, but not from the visceral cavities, display robust contractile behavior similar to lymphatic vessels from other animal models and humans. These differences are partially explained by L-type Ca2+ channel activity as revealed by the first measurements of murine lymphatic action potentials and contraction-associated Ca2+ transients.
  • 18.

    【2hr】Guidelines in Cardiovascular Research: Guidelines for measuring cardiac physiology in mice

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    机译 心血管研究指南：测量小鼠心脏生理的指南
    摘要：Cardiovascular disease is a leading cause of death, and translational research is needed to understand better mechanisms whereby the left ventricle responds to injury. Mouse models of heart disease have provided valuable insights into mechanisms that occur during cardiac aging and in response to a variety of pathologies. The assessment of cardiovascular physiological responses to injury or insult is an important and necessary component of this research. With increasing consideration for rigor and reproducibility, the goal of this guidelines review is to provide best-practice information regarding how to measure accurately cardiac physiology in animal models. In this article, we define guidelines for the measurement of cardiac physiology in mice, as the most commonly used animal model in cardiovascular research.Listen to this article’s corresponding podcast at .
  • 19.

    【2hr】Integrative Cardiovascular Physiology and Pathophysiology: Maximal strength training-induced improvements in forearm work efficiency are associated with reduced blood flow

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    机译 综合心血管生理学和病理生理学：最大强度训练所致前臂工作效率的提高与血流量减少有关
    摘要：Maximal strength training (MST) improves work efficiency. However, since blood flow is greatly dictated by muscle contractions in arms during exercise and vascular conductance is lower, it has been indicated that arms rely more upon adapting oxygen extraction than legs in response to the enhanced work efficiency. Thus, to investigate if metabolic and vascular responses are arm specific, we used Doppler-ultrasound and a catheter placed in the subclavian vein to measure blood flow and the arteriovenous oxygen difference during steady-state work in seven young men [24 ± 3 (SD) yr] following 6 wk of handgrip MST. As expected, MST improved maximal strength (49 ± 9 to 62 ± 10 kg) and the rate of force development (923 ± 224 to 1,086 ± 238 N/s), resulting in a reduced submaximal oxygen uptake (30 ± 9 to 24 ± 10 ml/min) and concomitantly increased work efficiency (9.3 ± 2.5 to 12.4 ± 3.9%) (all P < 0.05). In turn, the work efficiency improvement was associated with reduced blood flow (486 ± 102 to 395 ± 114 ml/min), mediated by a lower blood velocity (43 ± 8 to 32 ± 6 cm/s) (all P < 0.05). Conduit artery diameter and the arteriovenous oxygen difference remained unaltered. The maximal work test revealed an increased time to exhaustion (949 ± 239 to 1,102 ± 292 s) and maximal work rate (both P < 0.05) but no change in peak oxygen uptake. In conclusion, despite prior indications of metabolic and vascular limb-specific differences, these results reveal that improved work efficiency after small muscle mass strength training in the upper extremities is accompanied by a blood flow reduction and coheres with what has been documented for lower extremities.>NEW & NOTEWORTHY Maximal strength training increases skeletal muscle work efficiency. Oxygen extraction has been indicated to be the adapting component with this increased work efficiency in arms. However, we document that decreased blood flow, achieved by blood velocity reduction, is the adapting mechanism responding to the improved aerobic metabolism in the forearm musculature.
  • 20.

    【2hr】Integrative Cardiovascular Physiology and Pathophysiology: From ionic to cellular variability in human atrial myocytes: an integrative computational and experimental study

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    机译 整合性心血管生理学和病理生理学：从人心房肌细胞的离子变异到细胞变异：整合的计算和实验研究
    摘要：Variability refers to differences in physiological function between individuals, which may translate into different disease susceptibility and treatment efficacy. Experiments in human cardiomyocytes face wide variability and restricted tissue access; under these conditions, computational models are a useful complementary tool. We conducted a computational and experimental investigation in cardiomyocytes isolated from samples of the right atrial appendage of patients undergoing cardiac surgery to evaluate the impact of variability in action potentials (APs) and subcellular ionic densities on Ca2+ transient dynamics. Results showed that 1) variability in APs and ionic densities is large, even within an apparently homogenous patient cohort, and translates into ±100% variation in ionic conductances; 2) experimentally calibrated populations of models with wide variations in ionic densities yield APs overlapping with those obtained experimentally, even if AP characteristics of the original generic model differed significantly from experimental APs; 3) model calibration with AP recordings restricts the variability in ionic densities affecting upstroke and resting potential, but redundancy in repolarization currents admits substantial variability in ionic densities; and 4) model populations constrained with experimental APs and ionic densities exhibit three Ca2+ transient phenotypes, differing in intracellular Ca2+ handling and Na+/Ca2+ membrane extrusion. These findings advance our understanding of the impact of variability in human atrial electrophysiology.>NEW & NOTEWORTHY Variability in human atrial electrophysiology is investigated by integrating for the first time cellular-level and ion channel recordings in computational electrophysiological models. Ion channel calibration restricts current densities but not cellular phenotypic variability. Reduced Na+/Ca2+ exchanger is identified as a primary mechanism underlying diastolic Ca2+ fluctuations in human atrial myocytes.
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