Exogenous Hydrogen Sulfide (H2S) Reduces Blood Pressure and Prevents the Progression of Diabetic Nephropathy in Spontaneously Hypertensive Rats

Exogenous Hydrogen Sulfide (H2S) Reduces Blood Pressure and Prevents the Progression of Diabetic Nephropathy in Spontaneously Hypertensive Rats
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DOI:
10.3109/0886022x.2011.643365
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发表时间:
2012-01-01
期刊:
影响因子:
3
通讯作者:
Johns, Edward James
Johns, Edward James
中科院分区:
医学3区
文献类型:
--
作者:
Ahmad, Fiaz Ud Din;Sattar, Munavvar Abdul;Johns, Edward James

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高血压和糖尿病的并存导致肾病的快速发展。硫化氢(H_2S)被认为控制血管和肾功能。这项研究验证了外源性硫化氢降低糖尿病自发性高血压大鼠(SHR)血压和减缓肾病进展的假设。18只SHR分为三组:SHR组、SHR糖尿病组和SHR糖尿病组,对照组为正常血压非糖尿病大鼠。两组用链脲佐菌素(STZ)诱导糖尿病,一组给予硫化氢供体氢化钠(NaHS)治疗5周。在急性研究中,测量清醒和麻醉状态下的血压和肾皮质血流灌注量。在35天的时间里,在三个不同的场合测量了血浆和尿中的硫化氢水平、肌酐浓度和电解质。糖尿病SHR有较高的血压,较低的血浆和尿硫化氢水平,以及肾功能障碍,表现为血肌酐、肌酐清除量增加,尿钠钾比和肾皮质血流灌注量降低。NaHS降低血压,升高血浆和尿中H_2S水平,逆转STZ所致的肾功能障碍。这项研究的结果表明,外源性硫化氢可以降低SHR的血压,并对STZ诱导的肾病的进展起到保护作用。
The coexistence of hypertension and diabetes results in the rapid development of nephropathy. Hydrogen sulfide (H2S) is claimed to control the vascular and renal functions. This study tested the hypothesis that exogenous H2S lowers the blood pressure and decreases the progression of nephropathy in spontaneously hypertensive rats (SHR) that were diabetic. Eighteen SHR were divided into three groups: SHR, SHR diabetic, and SHR diabetic treated with a group of Wistar-Kyoto rats serving as normotensive nondiabetic control. Diabetes was induced with streptozotocin (STZ) in two groups and one diabetic group received sodium hydrosulfide (NaHS), a H2S donor for 5 weeks. Blood pressure was measured in conscious and anesthetized states and renal cortical blood perfusion in acute studies. Plasma and urinary H2S levels, creatinine concentrations, and electrolytes were measured on three different occasions throughout the 35-day period. Diabetic SHR had higher blood pressure, lower plasma and urinary H2S levels, and renal dysfunction as evidenced by increased plasma creatinine, creatinine clearance, and decreased urinary sodium-to-potassium ratio and renal cortical blood perfusion. NaHS reduced blood pressure, increased H2S levels in plasma and urinary excretion, and reversed the STZ-induced renal dysfunction. The findings of this study suggest that the administration of exogenous H2S lowers the blood pressure and confers protection against the progression of STZ-induced nephropathy in SHR.