Hyporeninemic Hypoaldosteronism in Diabetes Mellitus: Studies of the Autonomic Nervous System's Control of Renin Release

Abstract

The proposal that neurogenic mechanisms may contribute to suppressed plasma renin activity in diabetic patients with hyporeninemic hypoaldosteronism was examined. Five hyperkalemic, diabetic patients with mild to moderate renal insufficiency and evidence of autonomic or peripheral neuropathy were studied. Mean plasma renin (1.1 ± 0.2 ng/ml/h)andaldosterone(2.8 ± 0.8 ng/dl) values were low and showed minimal increase after a low-sodium diet. Sequential renin responses during 4 h upright posture were significantly diminished in all patients compared with control subjects. The normal increment in plasma norepinephrine after upright posture and exercise was also blunted in the patients. Infusion of the beta-adrenergic agonist isoproterenol at a dose to augment pulse rate by 20% of baseline produced a rapid twofold increase in renin in control subjects. The patients had no renin response to isoproterenol infusion at doses that elicited similar cardiovascular responses in both groups. These findings suggest that in hyporeninemic hypoaldosteronism associated with diabetes mellitus and neuropathy, an alteration in sympathetic nervous system activity may contribute to the decreased plasma renin levels. The diminished catecholamine response to upright posture could lead to a blunting of renin response during orthostasis and other maneuvers. Secondly, loss of renin response to isoproterenol infusion in the face of normal cardiovascular responses is consistent with a localized intrarenal defect at the beta-adrenergic receptor level or at more distal sites in patients with hyporeninemic hypoaldosteronism.