Differential Effects of an Angiotensin II Analogue on Pressor and Adrenal Receptors in the Rabbit

Abstract

The 1-sarcosine-8-alanine analogue of angiotensin II (1-Sar-8-Ala-angiotensin II) was infused at 1 and 5 µg/kg min^-1 into conscious rabbits on normal or sodium-deficient diets. Blood pressures during the control period were comparable in both groups; plasma renin activity, angiotensin II concentration, and aldosterone concentration were higher in the rabbits on the sodium-deficient diet than they were in the rabbits on the normal diet. The analogue caused a 6-mm Hg fall in mean arterial blood pressure in sodium-depleted rabbits. Plasma renin activity increased in both groups to eight to ten times the control values with the higher rate of infusion. Angiotensin II concentration paralleled plasma renin activity. Plasma aldosterone concentration increased after infusion of the analogue at 1 µg/kg min^-1 to three to four times the control values but decreased from these high levels after an additional 90-minute infusion at 5 µg/kg min^-1 to only one to two times the control values in both groups. Infusion of angiotensin II during the administration of the analogue caused a clear-cut increase in aldosterone concentration without a change in blood pressure. The persistence of elevated aldosterone levels during inhibitor blockade in the sodium-depleted rabbits does not prove that factors other than angiotensin participate in the aldosterone response to sodium deprivation. However, the data do indicate that 1-Sar-8-Ala-angiotensin II is a less effective antagonist of angiotensin II at the adrenal receptors than it is at the vascular smooth muscle receptors and suggest that the pressor and adrenal receptors differ.