A dose-response comparison of the actions of angiotensin II and angiotensin III in sheep

Abstract

Comparisons of aldosterone responses to [des-Asp1]-angiotensin II and angiotensin II, often at single dose levels, have shown a wide range of potency ratios. Therefore four-point dose-response comparisons were performed in sodium-replete sheep, using i.v. infusion rates of angiotension II and angiotensin II amide that reproduced the physiological range of blood concentration of angiotensin II for sheep. Angiotensin III was infused i.v. at the same rates. Effects on arterial blood pressure, cortisol secretion rate, adrenal blood flow and plasma levels of NA+ and K+ were also compared. The potency ratio, angiotensin III : angiotensin II amide, was 0.87 for actual aldosterone secretion rate and 0.90 for the calculated increase in aldosterone secretion. For angiotensin III : angiotensin II the ratios were 0.80 and 0.91 respectively. These ratios were not significantly different from 1.00 but the tendency for angiotensin II to be slightly more potent was probably due to a contribution from derived angiotensin III during infusion of angiotensin II. Angiotensin II or angiotensin II amide was approximately four times as potent as angiotensin III in raising arterial blood pressure. Cortisol secretion rate was slightly but significantly increased by all peptides at the higher infusion rates. Infusions had no effect on adrenal blood flow or plasma levels of Na+ but raised plasma levels of K+ slightly. These results confirm the conclusion from adrenal arterial infusion experiments that angiotensin II and III are almost equipotent in stimulating aldosterone secretion in sheep.