Inhibition of cGMP-associated pulmonary arterial relaxation to H2O2 and O2 by ethanol.
We have recently suggested that relaxation of isolated precontracted intrapulmonary arteries from calves to H2O2 or O2 may involve the activation of guanylate cyclase by peroxide metabolism via catalase. In this study, ethanol, an agent that modulates peroxide metabolism by catalase and selectively inhibits the activation of guanylate cyclase by H2O2 but not by nitric oxide-related activators, was employed to further investigate the role of catalase in pulmonary arterial relaxation and guanylate cyclase activation by O2 and H2O2. In precontracted pulmonary arteries, ethanol reverses H2O2-elicited relaxation and increases in guanosine 3',5'-cyclic monophosphate (cGMP) tissue levels without affecting similar responses to nitroprusside. The pulmonary arteries employed in this study show a hypoxic contraction that is associated with decreases in cGMP levels, and reoxygenation produces a somewhat phasic relaxation and a marked increase in cGMP levels. Ethanol produces an O2 tension-dependent contraction and reverses relaxation to reoxygenation associated with inhibition of O2-elicited increases in cGMP levels. Thus ethanol appears to function as a mimic of hypoxia by inhibiting relaxations elicited by O2. These findings support a hypothesized role for H2O2-dependent activation of guanylate cyclase in O2-dependent regulation of pulmonary arterial smooth muscle tone.
Burke-Wolin
T M
TM
Department of Physiology, New York Medical College, Valhalla 10595.
Wolin
M S
MS
D000818:Animals; D002417:Cattle; D006152:Cyclic GMP / Q000378:metabolism / Q000502:physiology*; D000431:Ethanol / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000860:Hypoxia / Q000503:physiopathology; D066298:In Vitro Techniques; D010100:Oxygen / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D014661:Vasoconstriction; D014664:Vasodilation / Q000187:drug effects*
D000431:Ethanol; D006861:Hydrogen Peroxide; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D010100:Oxygen