Vasoconstrictive effect of hydrogen sulfide involves downregulation of cAMP in vascular smooth muscle cells

Am J Physiol Cell Physiol. 2008 Nov;295(5):C1261-70. doi: 10.1152/ajpcell.00195.2008. Epub 2008 Sep 11.

Abstract

Hydrogen sulfide (H(2)S), a new endogenous mediator, produces both vasorelaxation and vasoconstriction. This study was designed to examine whether cAMP mediates the vasoconstrictive effect of H(2)S. We found that NaHS at a concentration range of 10-100 microM (yields approximately 3-30 microM H(2)S) concentration-dependently reversed the vasodilation caused by isoprenaline and salbutamol, two beta-adrenoceptor agonists, and forskolin, a selective adenylyl cyclase activator, in phenylephrine-precontracted rat aortic rings. Pretreatment with NaHS (10-100 microM) for 5 min also significantly attenuated the vasorelaxant effect of salbutamol and forskolin. More importantly, NaHS (5-100 microM) significantly reversed forskolin-induced cAMP accumulation in vascular smooth muscle cells. However, NaHS produced significant, but weaker, vasoconstriction in the presence of N(G)-nitro-l-arginine methyl ester (100 microM), a nitric oxide synthase inhibitor, or in endothelium-denuded aortic rings. Blockade of ATP-sensitive potassium channels with glibenclamide (10 microM) failed to attenuate the vasoconstriction induced by H(2)S. Taken together, we demonstrated for the first time that the vasoconstrictive effect of H(2)S involves the adenyly cyclase/cAMP pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclases / metabolism
  • Animals
  • Cell Line
  • Cyclic AMP / metabolism*
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Endothelium, Vascular / metabolism
  • Enzyme Inhibitors / pharmacology
  • Hydrogen Sulfide / metabolism*
  • KATP Channels / antagonists & inhibitors
  • KATP Channels / metabolism
  • Male
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / enzymology
  • Muscle, Smooth, Vascular / metabolism*
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / enzymology
  • Myocytes, Smooth Muscle / metabolism*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism
  • Potassium Channel Blockers / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction* / drug effects
  • Sulfides / pharmacology
  • Vasoconstriction* / drug effects
  • Vasoconstrictor Agents / pharmacology
  • Vasodilator Agents / pharmacology

Substances

  • Enzyme Inhibitors
  • KATP Channels
  • Potassium Channel Blockers
  • Sulfides
  • Vasoconstrictor Agents
  • Vasodilator Agents
  • Nitric Oxide
  • Cyclic AMP
  • Nitric Oxide Synthase
  • Adenylyl Cyclases
  • sodium bisulfide
  • Hydrogen Sulfide