Is there truly a sympathetic component to aldosterone hypertension?

Studies in rodents suggest that sympathetic activation may contribute to aldosterone (Aldo) hypertension (HT), but evidence in non‐rodent animals and in humans is equivocal. The goal of this study was to use complementary techniques to determine whether sympathetic activation contributes to HT induced by high circulating levels of Aldo. After control measurements, Aldo was infused IV for 14 days at 12μg/kg/day in 9 dogs maintained on a constant Na intake (~65 mmol/day). This increased plasma Aldo (control= 4.3±0.4 ng/dL) ~ 10‐fold and mean arterial pressure (MAP) from 103±2 to 121±5 mmHg. In addition, Aldo infusion was associated with marked polydipsea, increases in plasma osmolality (293±1 to 297±1 mOsm/kg H 2 0) and vasopressin (0.86±.32 to 1.73±0.34 pg/mL), hypokalemia (4.2±0.1 to 2.3±0.1) and suppression of PRA to undetectable levels. Despite these responses, there were no significant changes in plasma [norepinephrine], and depressor responses to ganglionic blockade with hexamethonium (5 mg, IV) were actually attenuated during Aldo HT, suggesting suppression of sympathetic activity. Finally, in 2 dogs, bilateral renal denervation failed to attenuate Aldo HT. In these dogs, MAP was 122 and 142 before and 122 and 144 two weeks after bilateral renal denervation. Thus, the failure of both global and renal specific measures to demonstrate sympathetic activation indicates that classic renal mineralocorticoid mechanisms account for the initial progression of HT produced by pathophysiological circulating levels of Aldo. HL‐51971