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硫化氢和替米沙坦处理可改善自发性高血压大鼠的血压和肾脏排泄反应。

Hydrogen sulphide and tempol treatments improve the blood pressure and renal excretory responses in spontaneously hypertensive rats.

机构信息

Department of Physiology, School of Pharmaceutical Sciences, Universiti Sains Malaysia , Penang , Malaysia .

出版信息

Ren Fail. 2014 May;36(4):598-605. doi: 10.3109/0886022X.2014.882218. Epub 2014 Feb 6.

Abstract

Oxidative stress and suppressed H2S production lead to increased renal vascular resistance, disturbed glomerular hemodynamics, and abnormal renal sodium and water handling, contribute to the pathogenesis and maintenance of essential hypertension in man and the spontaneously hypertensive rat. This study investigated the impact of H2S and tempol alone and in combination on blood pressure and renal hemodynamics and excretory functions in the SHR. Groups of WKY rats or SHR (n=6) were treated for 4 weeks either as controls or received NaHS (SHR+NaHS), tempol (SHR+Tempol), or NaHS plus tempol (SHR+NaHS +Tempol). Metabolic studies were performed on days 0, 14, and 28, thereafter animals were anaesthetized to measure renal hemodynamics and plasma oxidative and antioxidant markers. SHR control rats had higher mean arterial blood pressure (140.0 ± 2 vs. 100.0 ± 3 mmHg), lower plasma and urinary H2S, creatinine clearance, urine flow rate and urinary sodium excretion, and oxidative stress compared to WKY (all p<0.05). Treatment either with NaHS or with tempol alone decreased blood pressure and oxidative stress and improved renal hemodynamic and excretory function compared to untreated SHR. Combined NaHS and tempol therapy in SHRs caused larger decreases in blood pressure (∼20-22% vs. ∼11-15% and ∼10-14%), increases in creatinine clearance, urinary sodium excretion and fractional sodium excretion and up-regulated the antioxidant status compared to each agent alone (all p<0.05). These findings demonstrated that H2S and tempol together resulted in greater reductions in blood pressure and normalization of kidney function compared with either compound alone.

摘要

氧化应激和 H2S 生成抑制导致肾血管阻力增加、肾小球血液动力学紊乱和肾脏钠水代谢异常,从而促进人类和自发性高血压大鼠(SHR)原发性高血压的发病和维持。本研究探讨了 H2S 和替米沙坦单独及联合应用对 SHR 血压、肾血液动力学和排泄功能的影响。将 WKY 大鼠或 SHR(n=6)分为对照组或给予硫氢化钠(SHR+NaHS)、替米沙坦(SHR+Tempol)或硫氢化钠加替米沙坦(SHR+NaHS+Tempol)治疗 4 周。在第 0、14 和 28 天进行代谢研究,随后麻醉动物测量肾血液动力学和血浆氧化应激及抗氧化标志物。与 WKY 相比,SHR 对照组大鼠的平均动脉血压(140.0±2 对 100.0±3 mmHg)较高,血浆和尿 H2S、肌酐清除率、尿流率和尿钠排泄率以及氧化应激较低(均 P<0.05)。与未治疗的 SHR 相比,单独给予 NaHS 或替米沙坦均可降低血压和氧化应激,并改善肾血液动力学和排泄功能。与单独使用任一种药物相比,联合使用 NaHS 和替米沙坦治疗 SHR 可更大幅度地降低血压(分别约为 20-22%、11-15%和 10-14%),增加肌酐清除率、尿钠排泄和钠排泄分数,并上调抗氧化状态(均 P<0.05)。这些发现表明,与单独使用任一化合物相比,H2S 和替米沙坦联合使用可更大幅度地降低血压并使肾功能正常化。

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