Abstract
Hydrogen sulfide (H2S), a novel endogenous gaseous bioactive substance, has recently been implicated in the regulation of cardiovascular and neuronal functions. However, its role in the control of renal function is unknown. In the present study, incubation of renal tissue homogenates with l-cysteine (l-Cys) (as a substrate) produced H2S in a concentration-dependent manner. This H2S production was completely abolished by inhibition of both cystathionine β-synthetase (CBS) and cystathionine γ-lyase (CGL), two major enzymes for the production of H2S, using amino-oxyacetic acid (AOAA), an inhibitor of CBS, and propargylglycine (PPG), an inhibitor of CGL. However, inhibition of CBS or CGL alone induced a small decrease in H2S production. In anesthetized Sprague-Dawley rats, intrarenal arterial infusion of an H2S donor (NaHS) increased renal blood flow, glomerular filtration rate (GFR), urinary sodium (UNa·V), and potassium (UK·V) excretion. Consistently, infusion of both AOAA and PPG to inhibit the endogenous H2S production decreased GFR, UNa·V, and UK·V, and either one of these inhibitors alone had no significant effect on renal functions. Infusion of l-Cys into renal artery to increase the endogenous H2S production also increased GFR, UNa·V, and UK·V, which was blocked by AOAA plus PPG. It was shown that H2S had both vascular and tubular effects and that the tubular effect of H2S might be through inhibition of Na+/K+/2Cl- cotransporter and Na+/K+/ATPase activity. These results suggest that H2S participates in the control of renal function and increases urinary sodium excretion via both vascular and tubular actions in the kidney.
Footnotes
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This work was supported by the National Institutes of Health [Grants HL70726, DK54927]
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.108.149963.
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ABBREVIATIONS: H2S, hydrogen sulfide; l-Cys, l-cysteine; CBS, cystathionine β-synthetase; CGL, cystathionine γ-lyase; AOAA, aminooxyacetic acid; PPG, propargylglycine; GFR, glomerular filtration rate; U·V, urinary volume; UNa·V, urinary sodium; UK·V, urinary potassium; FF, fractional filtration; FENa, fractional excretion of sodium; FEK, fractional excretion of potassium; MAP, mean arterial blood pressure; NKCC, Na+/K+/2Cl- cotransporter; NCC, Na+/Cl- cotransporter; NKA, Na+/K+-ATPase; RBF, renal blood flow; ANOVA, analysis of variance; G, group; BM, basolateral membrane; HPLC, high-performance liquid chromatography; Kf, glomerular ultrafiltration coefficient.
- Received December 18, 2008.
- Accepted February 25, 2009.
- The American Society for Pharmacology and Experimental Therapeutics
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