Systemic circulatory adjustments to acute hypoxia and reoxygenation in unanesthetized sheep. Role of renin, angiotensin II, and catecholamine interactions.

Abstract

Abstract. The hemodynamic consequences of the hypoxic inhibition of angiotensin-converting enzyme activity were studied in chronically instrumented unanesthetized sheep (n = 8) breathing a hypoxic gas mixture for 60 min (Pao2 = 31 mm Hg) followed by reoxygenation with room air. Changes in cardiac output, vascular pressures, blood flow distribution, arterial pH, Paco2, Pao2, and arterial levels of plasma renin activity, angiotensin II, bradykinin, and catecholamines were measured at selected time points. Seven additional sheep underwent the same protocol but received saralasin, an angiotensin II receptor blocker beginning at 55 min of hypoxia and extending into the reoxygenation period. During hypoxia, both groups developed identical hemodynamic patterns including a rise in cardiac output (25%), blood pressure (15%), and preferential blood flow distribution to the heart, brain, adrenals, diaphragm, and skeletal muscle, as well as a decrease in the fraction of cardiac output to the kidneys and most ofthe gut. This was associated with a decrease in angiotensin II concentrations (from 35 to 17 pg/ml) in spite of a doubling in plasma renin activity and catecholamines. Bradykinin levels did not change. Upon reoxygenation, bolus production of angiotensin II (from 17 to 1,819 pg/ml) occurred in spite of a constant level of plasma renin activity. Concurrently, different he-

Endogenous angiotensin II inhibits production of cerebrospinal fluid during posthypoxemic reoxygenation in the rabbit.

“…1618 In contrast, angiotensin II levels have been reported to increase greatly during posthypoxic reoxygenation in sheep. 17 Thus, changes in endogenous levels of angiotensin II during and after hypoxia may influence the rate of CSF production and the development of intracranial hypertension.…”

“…33 During reoxygenation, plasma concentrations of angiotensin II quickly reach very high levels in sheep (approximately 1800 pg/mL). 17 Removal of the inhibition of angiotensin converting enzyme by reoxygenation may account for these abrupt large increases in plasma levels of angiotensin II. 17 In contrast to the previous findings in sheep, 17 plasma concentrations of angiotensin II did not increase during posthypoxic reoxygenation in the rabbit in this study.…”