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

Abstract

The coexistence of hypertension and diabetes results in the rapid development of nephropathy. Hydrogen sulfide (H 2 S) is claimed to control the vascular and renal functions. This study tested the hypothesis that exogenous H 2 S 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 H 2 S donor for 5 weeks. Blood pressure was measured in conscious and anesthetized states and renal cortical blood perfusion in acute studies. Plasma and urinary H 2 S 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 H 2 S 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 H 2 S levels in plasma and urinary excretion, and reversed the STZ-induced renal dysfunction. The findings of this study suggest that the administration of exogenous H 2 S lowers the blood pressure and confers protection against the progression of STZ-induced nephropathy in SHR.

Exogenous hydrogen sulfide protects H9c2 cardiac cells against high glucose-induced injury by inhibiting the activities of the p38 MAPK and ERK1/2 pathways

“…Changes in H 2 S levels in diabetes have attracted attention. There is clear evidence that circulating levels of H 2 S are reduced in animal models of diabetes (24,(35)(36)(37). Notably, lower circulating H 2 S levels have been measured in plasma samples obtained from patients with type 2 diabetes mellitus (T2DM) (35,38).…”

Hydrogen Sulfide Attenuates sFlt1-Induced Hypertension and Renal Damage by Upregulating Vascular Endothelial Growth Factor

“…Moreover, BP-lowering effects of H 2 S have also been previously reported in various other models of both experimental and spontaneous hypertension in rats. [38][39][40] It is known that H 2 S-induced vasorelaxation is mainly mediated by the opening of K ATP channels in vascular smooth muscle cells. 22 However, in this study, the antihypertensive effect of H 2 S is accompanied by an increase in plasma VEGF, which itself is a vasodilator.…”

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

“…H 2 S concentrations in the plasma or urine were measured spectrophotometrically and calculated against the calibration curve of standard H 2 S solutions (NaHS: 3.125-100 mM). 25 Creatinine clearance (Cr.Cl. ), fractional excretion of sodium (FE Na ), and absolute urinary sodium excretion (U Na V) were calculated using the standard equations.…”