Endothelium-dependent and independent cGMP mechanisms appear to mediate O2 responses in calf pulmonary resistance arteries.
Our laboratory has previously described in isolated 1- to 4-mm calf pulmonary arteries, an endothelium-independent contraction to hypoxia that appears to involve the removal of a H2O2-elicited guanosine 3',5'-cyclic monophosphate (cGMP)-mediated relaxation. In this study, we examined the effects of changes in O2 tension (PO2) on isolated endothelium-intact and endothelium-denuded calf pulmonary resistance arteries of approximately 200 microns in diameter. Resistance arteries precontracted with U46619 were found to undergo a contraction when exposed to a PO2 of 24-27 Torr (hypoxia) from a Po2 of 150 Torr (O2 atmosphere). This contraction was significantly larger in endothelium-intact than endothelium-removed arteries. In the intact artery, 30 microM nitro-L-arginine (NLA), an inhibitor of the biosynthesis of nitric oxide-like activators of guanylate cyclase, increased tone under O2 atmosphere and reduced the contraction to hypoxia to the level observed in the endothelium-removed artery. Reoxygenation caused a relaxation, which was not dependent on the endothelium or inhibited by NLA. The inhibitor of guanylate cyclase activation, LY83583 (10 microM), increased tone under O2 atmosphere, eliminated the contraction to hypoxia, and inhibited the relaxation to reoxygenation, whereas indomethacin (10 microM) did not alter these responses. Thus modulation of a cGMP mechanism, not involving the endothelium or metabolism of arginine, is a primary mediator of responses to changes in O2 tension, and the endothelium appears to cause an enhancement of the contraction to hypoxia via suppression by hypoxia of the tonic generation of an arginine-derived relaxing factor.
Omar
H A
HA
Department of Physiology, New York Medical College, Valhalla 10595.
Wolin
M S
MS
D000109:Acetylcholine / Q000494:pharmacology; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002417:Cattle; D006152:Cyclic GMP / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology* / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D007213:Indomethacin / Q000494:pharmacology; D019335:Nitroarginine; D010100:Oxygen / Q000097:blood*; D010313:Partial Pressure; D011448:Prostaglandin Antagonists; D011651:Pulmonary Artery / Q000502:physiology*; D014655:Vascular Resistance; D014661:Vasoconstriction; D014664:Vasodilation
D000634:Aminoquinolines; D011448:Prostaglandin Antagonists; D019335:Nitroarginine; C041715:6-anilino-5,8-quinolinedione; D001120:Arginine; D006152:Cyclic GMP; D000109:Acetylcholine; D010100:Oxygen; D007213:Indomethacin