Hemodynamic effects of arginine vasopressin in rats adapted to chronic hypoxia.
Acute and chronic pulmonary and systemic hemodynamic responses to arginine vasopressin (AVP) were examined in 4-wk hypoxia-adapted and air control rats. AVP, administered intravenously as bolus injections or sustained infusions, produced major dose-dependent V1-receptor-mediated reductions in mean pulmonary arterial pressure in hypoxia-adapted rats. These effects were comparable in pentobarbital-anesthetized, thoracotomized animals and in conscious, intact rats. Chronic infusions of AVP induced a sustained reduction in mean pulmonary arterial pressure and partially prevented the development of pulmonary hypertension without changing systemic arterial pressure. AVP induced significant decreases in cardiac output in both groups; the cardiac output response was not significantly different in hypoxia-adapted and air control animals. AVP induced almost no change in MPAP in air control rats. Furthermore the systemic pressor effects of AVP were significantly blunted in hypoxia-adapted rats compared with air controls. We conclude that the pulmonary depressor and blunted systemic pressor effects of AVP observed in hypoxia-adapted rats may be related to release of a vasodilator, such as endothelium-derived relaxing factor, vasodilator prostaglandins, or atrial natriuretic peptides. Further study is needed to elucidate these mechanisms and assess the usefulness of AVP and/or its analogues in the treatment and prevention of hypoxia-induced pulmonary hypertension.
Jin
H K
HK
Department of Medicine, University of Alabama, Birmingham 35294.
Yang
R H
RH
Chen
Y F
YF
Thornton
R M
RM
Jackson
R M
RM
Oparil
S
S
D000222:Adaptation, Physiological; D000758:Anesthesia; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002908:Chronic Disease; D003243:Consciousness; D006439:Hemodynamics / Q000187:drug effects*; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D010121:Oxytocin / Q000031:analogs & derivatives / Q000494:pharmacology; D011651:Pulmonary Artery / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains
D001127:Arginine Vasopressin; C047063:oxytocin, Phe(2)-Orn(8)-; D010121:Oxytocin