Hydrogen sulfide downregulates the aortic L-arginine/nitric oxide pathway in rats.
The aim of the present study was to investigate the effect of hydrogen sulfide (H(2)S) signaling by nitric oxide (NO) in isolated rat aortas and cultured human umbilical vein endothelial cells (HUVECs). Both administration of H(2)S and NaHS, as well as endogenous H(2)S, reduced NO formation, endothelial nitric oxide synthase (eNOS) activity, eNOS transcript abundance, and l-arginine (l-Arg) transport (all P < 0.01). The kinetics analysis of eNOS activity and l-Arg transport showed that H(2)S reduced V(max) values (all P < 0.01) without modifying K(m) parameters. Use of selective NOS inhibitors verified that eNOS [vs. inducible NOS (iNOS) and neuronal NOS (nNOS)] was the specific target of H(2)S regulation. H(2)S treatment (100 micromol/l) reduced Akt phosphorylation and decreased eNOS phosphorylation at Ser1177. H(2)S reduced l-Arg uptake by inhibition of a system y+ transporter and decreased the CAT-1 transcript. H(2)S treatment reduced protein expression of eNOS but not of nNOS and iNOS. Pinacidil (K(ATP) channel opener) exhibited the similar inhibitory effects on the l-Arg/NOS/NO pathway. Glibenclamide (K(ATP) channel inhibitor) partly blocked the inhibitory effect of H(2)S and pinacidil. An in vivo experiment revealed that H(2)S downregulated the vascular l-Arg/eNOS/NO pathway after intraperitoneal injection of NaHS (14 micromol/kg) in rats. Taken together, our findings suggest that H(2)S downregulates the vascular l-Arg/NOS/NO pathway in vitro and in vivo, and the K(ATP) channel could be involved in the regulatory mechanism of H(2)S.
Geng
Bin
B
Institute of Cardiovascular Research, First Hospital of Peking Univ., Beijing xishuku St. 8, 100034. bingeng@bjmu.edu.cn
Cui
Yuying
Y
Zhao
Jing
J
Yu
Fang
F
Zhu
Yi
Y
Xu
Geyang
G
Zhang
Zhiwen
Z
Tang
Chaoshu
C
Du
Junbao
J
D000393:Air Pollutants / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D001120:Arginine / Q000378:metabolism*; D002478:Cells, Cultured; D015536:Down-Regulation; D042783:Endothelial Cells / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013440:Sulfides / Q000494:pharmacology
D000393:Air Pollutants; D013440:Sulfides; D009569:Nitric Oxide; D001120:Arginine; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C025451:sodium bisulfide; D006862:Hydrogen Sulfide