Decreased adrenal responsiveness to angiotensin II: a defect present in spontaneously hypertensive rats. A possible model of human essential hypertension

Abstract

30% of patients with essential hypertension have a decreased adrenal response to angiotensin II (A II) on a low but not a high sodium intake. They also have a compensatory increase in the activity of the renin-angiotensin system best documented in a sodium-restricted state.To assess whether such a mechanism could account for the hypertension in genetically hypertensive rats, adrenal responsiveness to A II was determined in three groups of rats; spontaneously hypertensive rats (SHR), normotensive Wistar rats (WKY), and normotensive Sprague-Dawley rats (SDR). Animals in each group were placed on either a low or high sodium diet for 14 d with balance assessed by sodium excretion. The animals were then decapitated, blood was obtained for plasma renin activity (PRA), A II and aldosterone and adrenals isolated for the preparation of purified glomerulosa cells. The cells were incubated in Krebs-Ringer bicarbonate solution, containing bovine serum albumin, for 60 min in the absence and presence of increasing concentrations of A II. The PRA, basal aldosterone output, and adrenal sensitivity to A II were similar in the three groups of rats on the high sodium diet. On the low sodium diet the SHR had a significantly (P < 0.01) higher PRA (25+/-7 ng/ml per h) than either the WKY (12+/-2 ng/ml per h) or the SDR (7+/-1 ng/ml per h) and lower basal aldosterone output (68+/-17 vs. 154+/-43 and 197+/-21 ng/10(6) cells per h, respectively). In addition, the slope of the A II dose response curve was more shallow (P < 0.01) in the cells from the SHR than those obtained from the WKY and SDR.Thus, the SHR PRA and aldosterone responses to sodium restriction and aldosterone response to A II were similar to that previously described in a subgroup of patients with essential hypertension suggesting that the SHR will serve as a model for exploring the mechanism(s) responsible for the hypertension in these patients.