In vitro hypoxia on rat pulmonary artery: effects on contractions to spasmogens and role of KATP channels.
The effect of in vitro hypoxia for 1 h on concentration-response curves to vasoconstrictor spasmogens was examined in rat isolated pulmonary arteries. Hypoxia, like levcromakalim (KATP channel opener), did not affect contractions to endothelin-1 but attenuated contractions to U46619 ((1,5,5,)-hydroxy-11 alpha, 9 alpha-epoxymethano) prosta 5Z, 13E-dienoic acid; thromboxane-mimetic), angiotensin II, noradrenaline and 5-hydroxytryptamine. The attenuation was prevented by glybenclamide. In pre-contracted arteries, subsequent exposure to hypoxia caused a response consisting of four phases (transient relaxation due to endothelium-derived nitric oxide; transient contraction; slow relaxation; sustained contraction). Glybenclamide, if added before hypoxia, did not eliminate either of the relaxant phases but, if added during the sustained contractile phase, caused further contraction. We conclude that exposure of pulmonary arteries to prolonged hypoxia causes KATP channels to open, as in systemic arteries; this diminishes contractions to some, but not all, vasoconstrictor spasmogens. The data suggest that endothelin-1, unlike other vasoconstrictors, would remain a highly effective pulmonary vasoconstrictor under severe hypoxic conditions.
Wanstall
J C
JC
Department of Physiology and Pharmacology, University of Queensland, Brisbane, Australia.
O'Brien
E
E
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D019806:Cromakalim; D004347:Drug Interactions; D005905:Glyburide / Q000494:pharmacology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000503:physiopathology*; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D001578:Benzopyrans; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011450:Prostaglandin Endoperoxides, Synthetic; D011758:Pyrroles; D014662:Vasoconstrictor Agents; D019806:Cromakalim; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D005905:Glyburide