In vitro hypoxia attenuates vasorelaxation by potassium channel opening drugs and nitroprusside in isolated pulmonary arteries from rats.
The effects of in vitro hypoxia on relaxant responses to various vasodilator drugs were examined on norepinephrine-contracted ring preparations of rat pulmonary artery. The physiological salt solution that bathed the tissues was equilibrated with gas mixtures that contained 95%, 12%, 6%, 4% or 0% oxygen (oxygen tension of solution, > 650, 94, 44, 35 or < or = 11 mm Hg, respectively). Severe in vitro hypoxia (oxygen tension, 4 mm Hg) attenuated responses to pinacidil (negative log EC50 values: control, 5.61; hypoxia, 4.92). This effect of hypoxia was not prevented by endothelium removal or by indomethacin. Less severe hypoxia (oxygen tension < or = 35 mm Hg) attenuated responses to nitroprusside (negative log EC50: control, 8.34; hypoxia, 7.76). This effect of hypoxia was prevented by endothelium removal but not by indomethacin, NG-nitro-L-arginine methyl ester or the endothelin antagonist, cyclo(D-Trp-D-Asp-Pro-D-Val-Leu), and was not mimicked by endothelin. These effects of in vitro hypoxia were rapidly reversible and were distinct from the previously reported effects of chronic in vivo hypoxia on responses of pulmonary arteries to these drugs. It was also found that severe in vitro hypoxia abolished responses to acetylcholine and cromakalim and potentiated responses to sodium nitrite (negative log EC50: control, 3.79; hypoxia, 4.97) but had no effect on responses to colforsin (also known as forskolin).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Physiology and Pharmacology, University of Queensland, Brisbane, Australia.
J C
JC
Wanstall
D000818:Animals; D015687:Cell Hypoxia; D016232:Endothelins / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D006146:Guanidines / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology*; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects*; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D016232:Endothelins; D006146:Guanidines; D015221:Potassium Channels; D014665:Vasodilator Agents; D009599:Nitroprusside; D020110:Pinacidil