Mediators of alkalosis-induced relaxation in pulmonary arteries from normoxic and chronically hypoxic piglets.
Alkalosis-induced relaxation was measured in precontracted arterial rings from 1-wk-old piglets exposed to normoxia or to 3 days of chronic hypoxia. In normoxic piglet arteries, alkalosis-induced relaxation was blunted in arteries without functional endothelium and in arteries treated with nitric oxide synthase or guanylate cyclase inhibitors but not in arteries treated with cyclooxygenase inhibitors or Ca2+- and ATP-dependent K+-channel inhibitors. Inhibition of voltage-dependent K+ channels with 10(-3) M 4-aminopyridine also failed to block alkalosis-induced relaxation. 4-Aminopyridine at 10(-2) M did block the response, but this may have been due to sustained vascular smooth muscle depolarization. Arteries from hypoxic piglets exhibited greater contraction to the thromboxane mimetic U-46619, decreased endothelium-dependent relaxation, and blunted alkalosis-induced relaxation. The residual relaxation was eliminated by nitric oxide synthase but not by cyclooxygenase or voltage-dependent K+-channel inhibition. Alkalosis-induced relaxation of newborn piglet pulmonary arteries appears to be mediated by the nitric oxide-cGMP pathway and is attenuated after 3 days of hypoxia, likely because of decreased nitric oxide activity.
Gordon
J B
JB
Departments of Pediatrics and Neurology, Medical College of Wisconsin and Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin 53226, USA.
Halla
T R
TR
Fike
C D
CD
Madden
J A
JA
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000471:Alkalosis / Q000503:physiopathology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D002908:Chronic Disease; D004730:Endothelium, Vascular / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D000860:Hypoxia / Q000503:physiopathology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D026902:Potassium Channel Blockers; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology*; D012016:Reference Values; D013552:Swine; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology*
D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D014662:Vasoconstrictor Agents; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase