Activity of [Des-Aspartyl1]-Angiotensin II and Angiotensin II in Man

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Abstract
This study was designed to compare the effect of [des-Aspartyl1]-angiotensin II ([des-Asp]-A II) and angiotensin II (A II) on blood pressure and aldosterone production in man under conditions of normal and low sodium (Na) intake. Seven normal male subjects in balance on constant normal Na intake (UNa V 160.3±5.0 meq/24 h) for 5 days received A II and [des-Asp]-A II infusions on two consecutive days; 1 mo later they were restudied after 5 days of low Na intake (UNa V 10.5±1.6 meq/24 h). Each dose was infused for 30 min, sequentially. During normal Na intake, [des-Asp]-A II from 2 to 18 pmol/kg per min increased mean blood pressure from 85.2±3 to 95.3±5 mm Hg and plasma aldosterone concentration from 5.2±1.1 to 14.3±1.9 ng/100 ml. During low Na intake, the same dose of [des-Asp]-A II increased mean blood pressure from 83.7±3 to 86.7±3 mm Hg and plasma aldosterone concentration from 34.4±6.0 to 51.0±8.2 ng/100 ml. In contrast, A II from 2 to 6 pmol/kg per min during normal Na intake increased mean blood pressure from 83.3±4 to 102.3±4 mm Hg and plasma aldosterone concentration from 7.0±2.2 to 26.8±2.0 ng/100 ml; during low Na intake, A II increased mean blood pressure from 83.0±3 to 96.0±4 mm Hg and plasma aldosterone concentration from 42.0±9.7 to 102.2±15.4 ng/100 ml. A II and [des-Asp]-A II were equally effective in suppressing renin release. Plasma cortisol and Na and K concentration did not change. The effects of two doses (2 and 6 pmol/kg per min) of each peptide on blood pressure and aldosterone production were evaluated. During normal Na intake, [des-Asp]-A II had 11-36% of the pressor activity and 15-30% of the steroidogenic activity of A II. Na deprivation attenuated the pressor response and sensitized the adrenal cortex to both peptides, but the increase in steroidogenesis was greater with [des-Asp]-A II than with A II. The dose-response curves for [des-Asp]-A II with respect to blood pressure and aldosterone production were not parallel, and although no maximum was established for A II, [des-Asp]-A II was less efficacious. In summary, (a) [des-Asp]-A II has biologic activity in man, (b) [des-Asp]-A II is less efficacious than A II in stimulating aldosterone production, (c) Na deprivation sensitizes the adrenal cortex more markedly to [des-Asp]-A II than A II, and (d) dose-response curves for the two peptides differ, suggesting the possibility that they act at different receptor sites in vascular smooth muscle and the adrenal cortex.