The vasorelaxant effect of H(2)S as a novel endogenous gaseous K(ATP) channel opener

EMBO J. 2001 Nov 1;20(21):6008-16. doi: 10.1093/emboj/20.21.6008.

Abstract

Hydrogen sulfide (H(2)S) has been traditionally viewed as a toxic gas. It is also, however, endogenously generated from cysteine metabolism. We attempted to assess the physiological role of H(2)S in the regulation of vascular contractility, the modulation of H(2)S production in vascular tissues, and the underlying mechanisms. Intravenous bolus injection of H(2)S transiently decreased blood pressure of rats by 12- 30 mmHg, which was antagonized by prior blockade of K(ATP) channels. H(2)S relaxed rat aortic tissues in vitro in a K(ATP) channel-dependent manner. In isolated vascular smooth muscle cells (SMCs), H(2)S directly increased K(ATP) channel currents and hyperpolarized membrane. The expression of H(2)S-generating enzyme was identified in vascular SMCs, but not in endothelium. The endogenous production of H(2)S from different vascular tissues was also directly measured with the abundant level in the order of tail artery, aorta and mesenteric artery. Most importantly, H(2)S production from vascular tissues was enhanced by nitric oxide. Our results demonstrate that H(2)S is an important endogenous vasoactive factor and the first identified gaseous opener of K(ATP) channels in vascular SMCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arteries / drug effects
  • Arteries / metabolism
  • Blood Pressure / drug effects
  • Cardiovascular System / drug effects
  • Cell Separation
  • Cells, Cultured
  • Cystathionine gamma-Lyase / genetics
  • Cystathionine gamma-Lyase / metabolism
  • Cysteine / metabolism
  • Endothelium, Vascular / metabolism
  • Hydrogen Sulfide / administration & dosage*
  • Hydrogen Sulfide / metabolism
  • In Situ Hybridization
  • In Vitro Techniques
  • Injections, Intravenous
  • Male
  • Membrane Potentials / drug effects
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Nitric Oxide / pharmacology
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels / drug effects*
  • Potassium Channels / metabolism*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Vasodilation / drug effects
  • Vasodilation / physiology
  • Vasodilator Agents / administration & dosage*
  • Vasodilator Agents / metabolism
  • Vasomotor System / drug effects
  • Vasomotor System / physiology

Substances

  • Potassium Channel Blockers
  • Potassium Channels
  • RNA, Messenger
  • Vasodilator Agents
  • Nitric Oxide
  • Cystathionine gamma-Lyase
  • Cysteine
  • Hydrogen Sulfide