Hypertension in Primary Aldosteronism Is Initiated by Salt-Induced Increases in Vascular Resistance With Reductions in Cardiac Output.

Abstract

Few studies have investigated the hemodynamic mechanism whereby primary aldosteronism causes hypertension. The traditional view holds that hyperaldosteronism initiates hypertension by amplifying salt-dependent increases in cardiac output (CO) by promoting increases in sodium retention and blood volume. Systemic vascular resistance (SVR) is said to increase only as a secondary consequence of the increased CO and blood pressure. However, mounting evidence indicates that aldosterone can influence multiple pathways regulating vascular tone. We investigated the primary hemodynamic mechanism whereby hyperaldosteronism promotes salt sensitivity and initiation of salt-dependent hypertension. In unilaterally nephrectomized male Sprague-Dawley rats given infusions of aldosterone or vehicle, we used chronically implanted arterial pressure probes and Doppler ultrasonic flow probes to continuously monitor changes in mean arterial pressure, CO, and SVR 24 hours/day, 7 days/week in response to increases in salt intake. In vehicle-treated control rats, switching from a low-salt diet to a high-salt diet initiated modest increases in mean arterial pressure by increasing SVR while simultaneously decreasing heart rate and CO. In aldosterone-treated rats compared with control rats, switching from a low-salt diet to a high-salt diet initiated significantly greater increases in mean arterial pressure and SVR and significantly greater decreases in heart rate and CO. Aldosterone promoted salt sensitivity and initiation of salt-dependent hypertension by amplifying salt-induced increases in SVR while decreasing CO. Increases in CO are not required for the initiation or maintenance of hypertension. These findings challenge the traditional view of the hemodynamic mechanisms that cause hypertension in primary aldosteronism.