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Am J Physiol Regul Integr Comp Physiol (July 18, 2007). doi:10.1152/ajpregu.00207.2006
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Submitted on March 22, 2006
Accepted on June 27, 2007

Hydrogen Sulfide Downregulates the Aortic L-Arginine/Nitric Oxide Pathway in Rats

Bin Geng1*, YuYing Cui2, Jing Zhao3, Fang Yu3, Yi Zhu3, Geyang Xu4, Zhiwen Zhang5, Chaoshu Tang6, and Junbao Du7

1 First Hospital of Peking University, Institute of Cardiovascular Research, beijing, China; Department of Physiology, Peking University Health Science Center, beijing, China
2 First Hospital of Peking University, Institute of Cardiovascular Research, beijing, China
3 Department of Physiology, Peking University Health Science Center, beijing, China
4 Department of Physiology, Peking University Health Science Center, Bei Jing, China
5 Department of Physiology, Peking University Health Science Center, Beijing P.R., China
6 First Hospital of Peking University, Institute of Cardiovascular Research, Beijing P.R., China; Department of Physiology, Peking University Health Science Center, Beijing P.R., China
7 Department of Pediatrics, First Hospital of Peking University, Beijing P.R., China

* To whom correspondence should be addressed. E-mail: bingeng{at}bjmu.edu.cn.

The aim of the present study was investigation the effect of H2S signaling by nitric oxide (NO) in isolated rat aortas and cultured human umbilical vein endothelial cells (HUVECs). Both administration of H2S and NaHS as well as endogenous H2S reduced NO formation, eNOS activity, eNOS transcript abundance and L-Arg transport (all P<0.01). The kinetics analysis of eNOS activity and L-Arg transport showed that H2S reduced Vmax values (all P<0.01) without modifying Km parameters. Use of selective NOS inhibitors verified that eNOS (versus iNOS and nNOS) was the specific target of H2S regulation. H2S treatment (100 µmol/L) reduced Akt phosphorylation, and decreased eNOS phosphorylation at Ser1177. H2S reduced L-Arg uptake by inhibition of a system y+ transporter, and decreased the CAT-1 transcript. H2S treatment reduced protein expression of eNOS, but not of nNOS and iNOS. Pinacidil (KATP channel opener) exhibited the similar inhibitory effects on the L-Arg/NOS/NO pathway. Glibenclamide (KATP channel inhibitor) partly blocked the inhibitory effect of H2S and pinacidil. An in vivo experiment revealed that H2S down-regulated the vascular L-Arg/eNOS/NO pathway after intraperitoneal injection of NaHS (14 µmol/kg) in rats. Taken together, our findings suggest that H2S downregulates the vascular L-Arg/NOS/NO pathway in vitro and in vivo, and the KATP channel could be involved in the regulatory mechanism of H2S.




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T. Li, B. Zhao, C. Wang, H. Wang, Z. Liu, W. Li, H. Jin, C. Tang, and J. Du
Regulatory Effects of Hydrogen Sulfide on IL-6, IL-8 and IL-10 Levels in the Plasma and Pulmonary Tissue of Rats with Acute Lung Injury
Experimental Biology and Medicine, September 1, 2008; 233(9): 1081 - 1087.
[Abstract] [Full Text] [PDF]


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