Published Online
on May 19, 2003

A more recent version of this article appeared on July 1, 2003

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Submitted on September 5, 2002
Revised on September 22, 2002

Endothelin-1 and Vascular Tone in Subjects With Atherogenic Risk Factors

Anju Nohria; Leslie Garrett; Wendy Johnson; Scott Kinlay; Peter Ganz; and Mark A. Creager^*

From the Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.

^* To whom correspondence should be addressed. E-mail: mcreager{at}partners.org.

Abstract--Endothelin-1 (ET-1) is a potent vasoconstrictor that increases vascular tone in the resistance vessels of subjects with hypertension. It is unclear whether endogenous ET-1 affects resistance-vessel function equally in patients with other cardiovascular risk factors. Vasoconstriction to ET-1 is mediated principally via the endothelin-A (ET_A) receptor on vascular smooth muscle cells. Accordingly, we used an ET_A-specific antagonist, BQ-123, to test the hypothesis that endogenous ET-1 increases vascular resistance selectively in subjects with hypertension compared with other risk factors. BQ-123 was infused at 100 nmol/min for 80 minutes into the brachial artery of 10 subjects with hypertension (mean±SEM arterial pressure, 106±5 mm Hg), 12 subjects with hypercholesterolemia (mean±SEM total cholesterol, 7.1±0.2 mmol/L), 10 active smokers (mean±SEM, 42±11 pack-years), and 11 healthy, age-matched individuals. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. BQ-123 dilated resistance arterioles in hypertensive subjects, with FBF's increasing by 46±7% from baseline (P<0.001). BQ-123 increased FBF to a lesser extent in hypercholesterolemic (24±5%, P<0.001) and healthy (20±8%, P=0.007) individuals but did not affect FBF significantly in smokers (10±8%, P=0.185). The vasodilator response in hypertensive subjects, but not in hypercholesterolemic patients or smokers, was significantly greater than that in healthy individuals (P=0.012). Endogenous ET-1, acting via the ET_A receptor, increases resistance-vessel tone in subjects with hypertension more than in subjects with hypercholesterolemia or in smokers. These results indicate that ET-1 contributes more to the pathophysiology of hypertension than of other risk factors in subjects without overt atherosclerosis.

Key words: endothelin • endothelium • risk factors • hypertension, chronic • hypercholesterolemia • smoking

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