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(Circulation. 2001;103:263.)
© 2001 American Heart Association, Inc.

Clinical Investigation and Reports

Regulation of Plasma Endothelin by Salt in Salt-Sensitive Hypertension

Fernando Elijovich, MD; Cheryl L. Laffer, MD, PhD; Elias Amador, MD; Haralambos Gavras, MD; Margaret R. Bresnahan, DSc; Ernesto L. Schiffrin, MD, PhD, FRCPC

From the Section of Hypertension (F.E., C.L.L., E.A.), University of Texas Medical Branch at Galveston; Hypertension and Atherosclerosis Section (H.G., M.R.B.), Boston University School of Medicine, Boston, Mass; and the MRC Multidisciplinary Research Group on Hypertension (E.L.S.), Clinical Research Institute of Montreal, University of Montreal, Montreal, Quebec, Canada.

Correspondence to Fernando Elijovich, MD, Michigan State University, Medical Education and Research Center, 333 Bostwick Ave, Grand Rapids, MI 49503. E-mail Fernando_Elijovich{at}grmerc.net

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.

Key Words: endothelin • sodium • catecholamines • renin • hypertension

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