Role of cGMP mechanisms in response of rat pulmonary arteries to hypoxia.
We have demonstrated previously that in response to hypoxia, isolated rat pulmonary arteries show an initial endothelium-dependent relaxation followed by an endothelium-independent transient contraction. In the presence of increased extracellular Ca2+, both of these responses were enhanced in endothelium-intact arteries. Nitro-L-arginine, a blocker of the biosynthesis of endothelium-derived relaxing factor (EDRF), abolished the initial endothelium-dependent relaxation and Ca(2+)-induced enhancement of hypoxic contraction in endothelium-intact arteries but did not alter responses in endothelium-denuded vessels. Inhibition of prostaglandin formation with indomethacin had no effect on the hypoxia-elicited responses. Preincubation with LY 83583, an inhibitor of guanylate cyclase activation, abolished the initial hypoxia-elicited relaxation and subsequent contraction. M & B 22948, a guanosine 3',5'-cyclic monophosphate (cGMP) phosphodiesterase inhibitor, decreased tone under O2 but not under N2, causing an apparent enhancement of the contraction to hypoxia. Thus the modulation of hypoxic responses by the endothelium is dependent on changes in EDRF production, and a decrease in smooth muscle cGMP not involving an EDRF mechanism appears to mediate the endothelium-independent hypoxic contraction observed in the isolated rat pulmonary artery.
Mathew
R
R
Department of Pediatrics, New York Medical College, Valhalla, New York 10595.
Omar
H A
HA
Cherry
P D
PD
Gewitz
M H
MH
Wolin
M S
MS
D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D006152:Cyclic GMP / Q000502:physiology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019335:Nitroarginine; D011651:Pulmonary Artery / Q000503:physiopathology*; D011688:Purinones / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000634:Aminoquinolines; D011688:Purinones; D019335:Nitroarginine; C041715:6-anilino-5,8-quinolinedione; D001120:Arginine; C011145:zaprinast; D006152:Cyclic GMP; D007213:Indomethacin