The Influence of Sodium Intake on Physiological Responses to Angiotensin II in Conscious Dogs

Abstract

The renin-angiotensin system (RAS) is suppressed either by high sodium intake or by high levels of angiotensin II (A II). Therefore in prior studies it has been difficult to sort out the influence on the cardiovascular homeostases of different levels of A II and different levels of sodium in the diet respectively. The present study examines the quantitative effects of A II on mean arterial blood pressure (MABP), electrolyte excretion and hormone secretion in conscious dogs on low, normal and high sodium intake with the endogenous RAS blocked with continous intravenous infusion of enalapril (MK-421).

Fourteen dogs on three different Na diets, low, normal and high (5, 30 and 250 mmol/day), were infused continously with enalapril, 4 mg/kg/day and studied with superinfused A II at rates of 0, 1, 3, 6 and 12 ng/kg/min., each period lasting one week. Convening enzyme inhibitor (CEI) decreased MABP equally in dogs on low and normal sodium intake to about 80% of control, but did not have a significant effect in dogs on high sodium intake. The initial infusion of angiotensin II at the lowest rate had a pronounced effect on MABP in the normal and high sodium states, but had no effect on MABP in the sodium depleted dogs. However, at the higher rates of infusion, the angiotensin II increased the pressure to a similar degree at all levels of sodium intake. All four dogs in the high sodium group developed circulatory difficulties at the 6 or 12 ng level of A II infusion: One hemorrhaged in the feces, one developed congestive failure, and in the other two the arterial pressure remained elevated an average of 23 mm Hg after removal of all drugs. Plasma renin activity increased in all groups after CEI; however, renin secretion was suppressed by much smaller rates of angiotensin II infusion in the normal and sodium loaded dogs than in the sodium depleted dogs. CEI suppressed plasma aldosterone 30% in the low sodium dogs but by a lesser percentage in the normal sodium dogs; plasma aldosterone increased in all groups after A II. The present study indicates that when the endogenous RAS is blocked with CEI, small increments in angiotensin II infusion rate can cause almost linear increments in the chronic level of mean arterial pressure at varying levels of sodium intake. Also A II infusion and high dietary sodium can have independent effects on both plasma renin activity and plasma aldosterone concentration.