Regulation of plasma endothelin by salt in salt-sensitive hypertension

Abstract

Background - Salt dependency of blood pressure (BP) characterizes most models of experimental hypertension in which endothelins play a significant vasoconstrictor role. Despite this, there are no data on the regulation of plasma endothelin by salt balance in human hypertension. Methods and Results - Plasma endothelin was measured in 47 patients with essential hypertension. Endothelin, catecholamine, and plasma renin activity (PRA) responses to 24-hour sodium deprivation (↓, Na) were assessed in 29 of these patients. Endothelin was higher in hypertensive patients (4.6±0.2 fmol/mL) than in 20 control subjects (3.3±0.3 fmol/mL, P<0.002), was correlated with BP, and was negatively associated with PRA (P<0.04). Salt-sensitive, salt-resistant, and indeterminate groups were defined by the tertiles of the t statistic for the difference in BP before and after ↓ Na. Systolic BP falls were -15±1, -2±2, and -9±1 mm Hg, respectively. PRA, its response to ↓ Na, and its level after ↓ Na were lowest (albeit nonsignificant) in salt-sensitive patients. Baseline catecholamine and endothelin levels did not differ among the groups. In response to ↓ Na, catecholamines increased more significantly in salt-sensitive patients (+2.4±0.9 nmol/L) than in the other groups (0.4±0.2 and 0.7±0.2 nmol/L for indeterminate and salt-resistant groups, respectively; P<0.03), whereas endothelin increased in the salt-sensitive group (0.8±0.3 fmol/mL), decreased in the salt-resistant group (-0.4±0.3 fmol/mL), and sustained minimal change in the indeterminate group (0.2±0.3 fmol/mL) (P<0.04). Thus, endothelin levels in the salt-depleted state were highest in salt-sensitive patients (5.2±0.4 fmol/mL) versus the other groups (3.4±0.4 and 4.4±0.4 fmol/mL for salt-resistant and indeterminate groups, respectively) (P<0.02). Changes in endothelin during ↓ Na and levels after ↓ Na were correlated with changes in catecholamines (P<0.02). Conclusions - Our data suggest that salt-depleted salt-sensitive hypertensives with blunted renin responses exhibit enhanced catecholamine-stimulated endothelin levels and may therefore respond better than unselected patients with essential hypertension to endothelin receptor blockers.