Hypereninemic hypoaldosteronism in association with neoplasia induced hypercalcemia in the Fischer rat

Abstract

Neoplasia induced hypercalcemia in the Fischer rat model is associated with the development of systolic hypertension at one week after transplantation of a Leydig cell tumor. To investigate the renin-aldosterone system in the hypertensive hypercalcemic Fischer rat the plasma renin activity (PRA), plasma aldosterone (PA), PRA, and systolic blood pressure (BP) responses to immobilization stress, the PA and corticosterone responses to infusion of graded doses of ACTH and the PA and BP responses to graded doses of angiotensin II (AII) were evaluated at 12 days in tumor transplanted rats and in controls. Serum calcium (17 ± 0.9 mg/dl) and basal PRA (21.7 ± 3.9 ng/ml · h −1) in the tumor transplanted rats were higher ( p < 0.001) than the serum calcium (10.3 ± 0.3 mg/dl) and basal PRA (3.4 ± 0.8 ng/ml · h −1) in the controls. Basal systolic blood pressure was higher ( p < 0.01) in the tumor transplanted rats (117 ± 3.7 mm Hg) than the controls (106 ± 2.8 mm Hg). Serum calcium and basal PRA were positively correlated (γ = 0.74, p < 0.025). Basal plasma aldosterone levels were less ( p < 0.01) in the tumor transplanted rats (3.9 ± 1.0 ng/dl) than in the controls (8.1 ± 1.2 ng/dl). Although PRA responses to immobilization stress were greater ( p < 0.01) in the tumor rats, PA responses were less ( p < 0.01) in the tumor transplant group. PA and corticosterone responses to ACTH were less ( p < 0.05) in the tumor transplant rats, and PA responses to AII were markedly ( p < 0.001) suppressed in the tumor group. PA responses to infusion of 48 ng/kg/min AII were negatively correlated ( γ = −0.74, p < 0.025) with ambient serum calcium levels. BP responses to both immobilization stress and AII were greater ( p < 0.01) in the tumor transplanted rats than the controls. BP responses to stress and to AII were positively correlated with calcium concentrations. Elevated calcium levels may contribute to the development of hypertension by increasing vasoactive responses to pressor factors such as angiotensin. A hypereninemic hypoaldosterone state develops in association with neoplasia-induced hypercalcemia in the Fischer rat.