Production and actions of hydrogen sulfide, a novel gaseous bioactive substance, in the kidneys.
Hydrogen sulfide (H(2)S), 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 H(2)S in a concentration-dependent manner. This H(2)S production was completely abolished by inhibition of both cystathionine beta-synthetase (CBS) and cystathionine gamma-lyase (CGL), two major enzymes for the production of H(2)S, 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 H(2)S production. In anesthetized Sprague-Dawley rats, intrarenal arterial infusion of an H(2)S donor (NaHS) increased renal blood flow, glomerular filtration rate (GFR), urinary sodium (U(Na) x V), and potassium (U(K) x V) excretion. Consistently, infusion of both AOAA and PPG to inhibit the endogenous H(2)S production decreased GFR, U(Na) x V, and U(K) x 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 H(2)S production also increased GFR, U(Na) x V, and U(K) x V, which was blocked by AOAA plus PPG. It was shown that H(2)S had both vascular and tubular effects and that the tubular effect of H(2)S might be through inhibition of Na(+)/K(+)/2Cl(-) cotransporter and Na(+)/K(+)/ATPase activity. These results suggest that H(2)S participates in the control of renal function and increases urinary sodium excretion via both vascular and tubular actions in the kidney.
Xia
Min
M
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, P.O. Box 980613, Richmond, VA 23298, USA.
Chen
Li
L
Muh
Rachel W
RW
Li
Pin-Lan
PL
Li
Ningjun
N
D000818:Animals; D027682:Cation Transport Proteins / Q000187:drug effects / Q000378:metabolism; D003541:Cystathionine beta-Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000037:antagonists & inhibitors / Q000378:metabolism; D003545:Cysteine / Q000378:metabolism / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006862:Hydrogen Sulfide / Q000378:metabolism* / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D007672:Kidney Cortex / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000378:metabolism; D013440:Sulfides / Q000494:pharmacology
D027682:Cation Transport Proteins; D004791:Enzyme Inhibitors; D013440:Sulfides; D012964:Sodium; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; C025451:sodium bisulfide; D003545:Cysteine; D006862:Hydrogen Sulfide