ANGIOTENSIN-II MODULATES RESPIRATORY AND ACID-BASE RESPONSES TO PROLONGED HYPOXIA IN CONSCIOUS DOGS

We tested the hypothesis that angiotensin II(ANG II) contributes to ve ntilatory and acid-base adaptations during 3-4 h of hypoxia (partial p ressure of O-2 in arterial blood approximate to 43 Torr) in the consci ous dog. Three protocols were carried out over 3-4 h in five dogs: 1) air control, 2) 12% O-2 breathing, and 3) 12% O-2 breathing with ANG I I receptors blocked by infusion of saralasin (0.5 mu g kg(-1).min(-1)) . After 2 h of hypoxia, expired ventilation and alveolar ventilation p rogressively increased, and the partial pressure of CO2 in arterial bl ood and the difference between the arterial concentrations of strong c ations and strong anions ([SID]) decreased. When the hypoxic chemorece ptor drive to breathe was abolished transiently for 30 s with 100% O-2 , the resultant central apneic time decreased between 0.5 and 2.5 h of hypoxia. All these adaptive responses to hypoxia were abolished by AN G II receptor block. Because plasma ANG II levels were lower during hy poxia and hypoxic release of arginine vasopressin from the pituitary i nto the plasma was prevented by ANG II receptor block, the brain renin -angiotensin system was likely involved. It is possible that ANG II me diates ventilatory and acid-base adaptive responses to prolonged hypox ia via alterations in ion transport to decrease [SID] in brain extrace llular fluid rather than acting by a direct neural mechanism.