title: Direct inhibition of endothelial nitric oxide synthase by hydrogen sulfide: contribution to dual modulation of vascular tension.
abstract: We characterized actions of hydrogen sulfide (H(2)S) on tension of isolated rat and mouse aortae, and then examined if H(2)S could directly modulate activity of endothelial nitric oxide (NO) synthase (eNOS). Isometric tension was recorded in rat and mouse aortic rings. Activity of recombinant bovine eNOS was determined as conversion of [(3)H]-arginine into [(3)H]-citrulline. NaHS, a H(2)S donor, caused contraction at low concentrations and relaxation at high concentrations in both rat and mouse aortae precontracted with phenylephrine. The contractile and relaxant effects of NaHS were enhanced and partially blocked, respectively, by the K(+)(ATP) channel inhibitor glibenclamide in the rat, but not mouse, aortae. In the KCl-precontracted rat aorta, NaHS produced glibenclamide-resistant contraction and relaxation. NaHS produced only relaxation, but not contraction, in the endothelium-denuded aortae, and also in the endothelium-intact aortae in the presence of inhibitors of NOS or soluble guanylate cyclase. NaHS pretreatment greatly attenuated the relaxation induced by acetylcholine, but not by an NO donor, in the tissues. Finally, we found that NaHS inhibited the conversion of [(3)H]-arginine into [(3)H]-citrulline by recombinant eNOS. NaHS thus causes contraction and relaxation in rat and mouse aortae. K(+)(ATP) channels are considered to contribute only partially to the NaHS-evoked relaxation. Most interestingly, our data demonstrate direct inhibition of eNOS by NaHS, probably responsible for its contractile activity, being evidence for a novel function of H(2)S.
authors.affiliation: Division of Physiology and Pathophysiology, School of Pharmacy, Kinki University, 3-4-1 Kowakae, Higashi-Osaka, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Kubo
authors.forename: Ichiko
authors.initials: I
authors.lastname: Doe
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kurokawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nishikawa
authors.forename: Atsufumi
authors.initials: A
authors.lastname: Kawabata
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000393:Air Pollutants / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors* / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000393:Air Pollutants; D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D052250:Nitric Oxide Synthase Type III; D006162:Guanylate Cyclase; D000109:Acetylcholine; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester; D006862:Hydrogen Sulfide