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. Recently, 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 found that aldosterone promoted salt sensitivity and initiation of salt-dependent hypertension by amplifying salt-induced increases in SVR while decreasing CO. These findings challenge the traditional view of the hemodynamic mechanisms that cause salt-sensitive hypertension in primary aldosteronism.
Michal Pravenec, PhD., DSc.
Research of Dr. Pravenec was focused on the role of genetic determinants in the pathogenesis of features of the metabolic syndrome in the spontaneously hypertensive rat (SHR) using a combination of gene expression profiles as intermediary phenotypes between variability at DNA level and complex metabolic traits. The results of integrated genetic and correlation analyses using recombinant inbred and genetically modified SHR strains led to identification of the first quantitative trait loci (QTLs) at the molecular level, including mutated Cd36, Ogn, Endog, Ebi2, Wars2, Folr1, Gstm1, Srebf1 and other genes as determinants of metabolic or hemodynamic traits. In recent years, research is also focused on pathophysiological mechanisms that predispose to salt-dependent hypertension by formulating and testing the vasodysfunction theory.