Importance of Circulating Angiotensin Ii for Elevation of Arterial Pressure During Acute Hypercapnia in Anaesthetized Dogs

SUMMARY 1. In anaesthetized dogs acute hypercapnia produced by ventilation with 10% CO 2 in air caused release of vasoactive substances and changes of arterial pressure. Catecholamines, angiotensin II, bradykinin and prostaglandin‐like substances were bioassayed continuously in arterial blood using the blood‐bathed organ technique of Vane. 2. Acute hypercapnia in control dogs causes responses of rat stomach strip, chick rectum and rat colon indicating initial release of noradrenaline, followed by angiotensin II, and occasionally release of prostaglandin‐like substances into the circulation. 3. The initial transient, pressor response to hypercapnia coincided with the appearance of noradrenaline, and the secondary progressive rise in arterial pressure was accompanied by increased circulating angiotensin II. 4. In dogs treated with the angiotensin converting enzyme inhibitor SQ 20881 (1–2 mg/kg, i.v.), hypercapnia did not cause the secondary elevation of arterial pressure despite pronounced elevation of noradrenaline levels in the circulation. Increased arterial concentrations of bradykinin of less than 1 ng/ml, assayed by a strip of cat jejunum, were detected during hypercapnia in four out of six dogs treated with SQ 20881, but not in untreated dogs. 5. Intravenous infusion of the angiotensin antagonist [Sar 1 ‐Ile 8 ]‐angiotensin II (0.5–1.0 μg/kg per min) attenuated the secondary pressor response to hypercapnia and abolished the contractions of rat colon produced by hypercapnia and angiotensin II. 6. The results indicate that adrenergic stimulation may be responsible for the transient pressor response on induction of hypercapnia, but elevation of angiotensin II activity in the circulation is of major importance for mediating the secondary progressive rise in arterial pressure during the later stage of acute respiratory acidosis. 7. After inhibition of angiotensin converting enzyme, hypercapnia reduces arterial pressure, not only because the vasoconstrictor effect of angiotensin has been removed, but also because inhibition of pulmonary kininase may allow vasodilator kinins to reach the arterial circulation.