Biological Activity of High Dose of Des-Asp1-,Ileu8-Angiotensin Ii in Man

Abstract

The biological activity of high doses of des-asp1-,ileu8-angiotensin II (AIIIA) was studied in man. In 5 normal men an intravenous infusion of 600 ng/kg/min of AIIIA for 30 min caused a slight rise in blood pressure, a decrease in plasma renin activity and an increase in plasma aldosterone. This dose inhibited pressor and steroidogenic actions of angiotensin II infused into the same 5 normal men at a rate of 20 ng/kg/min for 30 min. These results are considerably different from our previous report using lower dose (200 ng/kg/min) of AIIIA and indicate that in man AIIIA has both agonist and antagonist activities on the peripheral arterioles as well as on the adrenal cortex.

Lack of inhibition of ACTH-induced aldosterone stimulation by Desasp-, ileu-angiotensin II in man.

“…An increase in PA induced by AIIIA infusion is thought to be due to an agonistic action of AIIIA on the aderenal cortex as suggested previously (Kono et al, 1976b;Kono et al, 1977). A decrease in PRA by AMA may be due to the direct inhibition of renin release in addition to the negative feedback inhibition resulting from the rise in BP (Kono et al, 1977).…”

“…Based on this observation, the design of Experiment3was made. In our previous study (Kono et al, 1977) an intravenous infusion of600ng/kg/min of AIIIA inhibited pressor and steroidogenic effects of AII infused simultaneously at a rate of20ng/kg/min in5normal men. In Experiment3of the present study the same dose of AIIIA did not inhibit the ACTHinduced increase in PA in5normal men.…”

“…Both All and ACTH accelerate the convertion of cholesterol to pregnenolone in adrenocortical steroid hormone synthesis and this may account for an increase in aldosterone (Burwell et al, 1969). However, All is thought to stimulate zona glomerulosa cells selectively and does not stimulate cortisol secretion in man (Kono et al, 1975) On the other hand, ACTH is thought to stimulate mainly zona fasciculata-reticularis and the precise mechanism of aldosterone stimulation by ACTH is still unknown.…”

“…Plasma aldosterone (PA) and plasma cortisol (PC) were measured by radioimmunoassay (Kona et al, 1976a: Kono et al, 1975 before, 30, 45, and 60min after the injection.…”

“…Plasma renin activity (PRA) was also measured by radioimmunoassay (Kono et al, 1974) before and45min after the injection. Blood pressure (BP) was checked before and after the ACTH injection.…”