Pharmacologic properties of isolated proximal pulmonary arteries after seven-day exposure to in vivo hyperoxia.
Marked damage to the endothelium is associated with the pulmonary hypertension that develops during in vivo exposure to hyperoxia at normobaric pressures. We hypothesized that endothelial cell damage may contribute to initial increases in vascular tone during the development of hypertension by altering the metabolism of vasoactive compounds and/or modulating vessel responses to those agents that require an intact endothelium for their actions. This study reports the effects of in vivo hyperoxic damage to the lung on the pharmacologic properties of isolated pulmonary vessels. Proximal pulmonary arteries isolated from adult and weanling rats that breathed 85% O2 for 7 days were studied using myograph techniques. Isometric tension development was recorded in response to the cumulative addition of prostaglandin F2 alpha (PGF2 alpha) and the ability of acetylcholine (ACh) to relax precontracted vessels was subsequently assessed. Sensitivities to PGF2 alpha were increased in both adult and weanling hyperoxic vessels relative to control. Conversely, relaxation to acetylcholine was reduced following hyperoxic injury. Control vessels relaxed completely to acetylcholine addition, while only a 30% relaxation was recorded in adult hyperoxic arteries and a 50% relaxation was measured in weanling hyperoxic tissues. This effect on vasodilation was specific for the endothelium-dependent dilator ACh. By contrast, relaxation responses to sodium nitroprusside and papaverine, endothelium-independent agonists, were unaffected following hyperoxic injury. These results demonstrate that in vivo exposure to high O2 concentrations increases the sensitivity of isolated pulmonary arteries to the vasoconstrictor PGF2 alpha and markedly diminishes the ability of ACh to relax precontracted pulmonary vessels.(ABSTRACT TRUNCATED AT 250 WORDS)
Coflesky
J T
JT
Department of Physiology and Biophysics, University of Vermont, College of Medicine, Burlington 05405.
Evans
J N
JN
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D015237:Dinoprost / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000503:physiopathology / Q000648:ultrastructure; D000860:Hypoxia / Q000473:pathology / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008855:Microscopy, Electron, Scanning; D011651:Pulmonary Artery / Q000187:drug effects* / Q000503:physiopathology / Q000648:ultrastructure; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014664:Vasodilation
D015237:Dinoprost; D000109:Acetylcholine