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Indapamide-induced prevention of myocardial fibrosis in spontaneous hypertension rats is not nitric oxide-related

机译:吲达帕胺诱导的自发性高血压大鼠心肌纤维化的预防与一氧化氮无关

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We studied the effect of thiazide-like diuretic - indapamide on fibrosis development in the left ventricle of young spontaneously hypertensive rats (SHR) and assessed the involvement of nitric oxide in this process. Six-week-old male SHR were treated with indapamide (1 mg/kg/day) for six weeks. Age-matched SHR were used as hypertensive and Wistar-Kyoto rats (WKY) as normotensive control. Systolic blood pressure was measured by tail-cuff plethysmography. Nitric oxide synthase (NOS) activity, protein expressions of endothelial (eNOS) and inducible NOS (iNOS), myocardial fibrosis and collagen type I and III were determined in the left ventricle. Indapamide treatment partially prevented SBP increase in SHR (SHR+Indapamide: 157 +/- 4, SHR: 171 +/- 3, WKY: 119 +/ 3 mmHg). Indapamide prevented myocardial fibrosis development in SHR, but without affecting collagen type I to type III ratio. Indapamide did not affect NOS activity as well as eNOS and iNOS protein expressions in the left ventricles evaluated by both Western blot and immunohistochemically. In conclusion, our results indicate that indapamide-induced prevention of myocardial fibrosis is not mediated by nitric oxide-related mechanism.
机译:我们研究了噻嗪类利尿剂-吲达帕胺对年轻自发性高血压大鼠(SHR)左心室纤维化发展的影响,并评估了一氧化氮在这一过程中的参与。六周大的男性SHR用吲达帕胺(1 mg / kg /天)治疗六周。年龄匹配的SHR用作高血压大鼠,Wistar-Kyoto大鼠(WKY)用作血压正常对照。通过尾袖式容积描记法测量收缩压。测定左心室中一氧化氮合酶(NOS)的活性,内皮蛋白(eNOS)和诱导型NOS(iNOS)的蛋白表达,心肌纤维化以及I型和III型胶原。吲达帕胺治疗部分阻止了SHR的SBP升高(SHR + Indapamide:157 +/- 4,SHR:171 +/- 3,WKY:119 + / 3 mmHg)。吲达帕胺可预防SHR中心肌纤维化的发展,但不会影响I型胶原与III型胶原的比率。通过蛋白质印迹和免疫组织化学评估,吲达帕胺不会影响左心室的NOS活性以及eNOS和iNOS蛋白表达。总之,我们的结果表明吲达帕胺诱导的心肌纤维化的预防不是由一氧化氮相关的机制介导的。

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