Bicarbonate-dependent effect of hydrogen sulfide on vascular contractility in rat aortic rings.
Hydrogen sulfide (H(2)S), an endogenous gaseous mediator, produces both vasorelaxation and vasoconstriction at different concentrations. We found in the present study that NaHS, an H(2)S donor, produced stronger vasorelaxant and weaker vasoconstrictive effects in HEPES solution compared with those achieved in Krebs solution. We further screened the buffer components and found that bicarbonate (HCO(3)(-)) was the ion to influence the effect of H(2)S. After examining the vasorelaxant effects of acetylcholine, a vasodilator by releasing nitric oxide, and isoprenaline, a β-adrenoceptor agonist, in HEPES and Krebs buffers, we found the HCO(3)(-)-dependent effect was specific to H(2)S. Blockade of anion exchanger-2 activity with 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) or with HCO(3)(-)-free solution abolished the vasoconstrictive effect of NaHS. Moreover, NaHS decreased nitric oxide level in the rat aorta in HCO(3)(-)-containing buffer, but this effect was abolished by HCO(3)(-)-free buffer or DIDS. In summary, we found for the first time that H(2)S stimulates anion exchanger to transport extracellular HCO(3)(-) in exchange for intracellular superoxide anions, which may further inactivate nitric oxide and induces vasoconstriction.
Liu
Yi-Hong
YH
Department of Pharmacology, Yong Loo Lin School of Medicine, National Univ. of Singapore, 117597 Singapore.
Bian
Jin-Song
JS
D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000393:Air Pollutants / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001639:Bicarbonates / Q000494:pharmacology*; D002021:Buffers; D004594:Electrophysiology; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D007202:Indicators and Reagents / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D000393:Air Pollutants; D001639:Bicarbonates; D002021:Buffers; D007202:Indicators and Reagents; D009569:Nitric Oxide; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D000420:Albuterol; D006862:Hydrogen Sulfide