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(Hypertension. 2003;42:43.)
© 2003 American Heart Association, Inc.

Scientific Contributions

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

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

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

Correspondence to Mark A. Creager, MD, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115. E-mail mcreager{at}partners.org

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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