Blunted effects of endothelin upon small subcutaneous resistance arteries of mild essential hypertensive patients


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Abstract

Objective: In experimental models of hypertension in the rat, resistance arteries present a blunted response to endothelin, a potent vasoconstrictor peptide. The primary objective of this study was to investigate whether, as in hypertensive rat blood vessels, the response of human resistance arteries to endothelin was altered in essential hypertensive patients, in order to further understand the possible physiopathological involvement of this peptide in human hypertensionDesign: Normotensive male subjects and sex- and age-matched mild essential hypertensive patients who had not received antihypertensive drugs for more than 6 months were investigatedMethods: Small arteries were dissected from gluteal subcutaneous biopsies and mounted on a wire-myograph. Blood vessels were measured and dose-response curves to different agents testedResults: The external diameter of blood vessels of the hypertensive patients tended to be smaller and the width of their media tended to be thicker, but the cross-sectional area of the wall was similar in both groups. Lumen diameters were significantly smaller in hypertensives and the media: lumen ratio was significantly increased in hypertensive patients. Active tension responses and sensitivity to norepinephrine, arginine vasopressin and angiotensin II were similar in both groups, but calculated active pressure responses were enhanced in hypertensives due to the smaller blood vessel lumen. Tension responses to endothelin-1 at increasing concentrations of 0.1 to 100nmol/l were lower in hypertensive patients, but the calculated transmural active pressure developed was not significantly different at or above 10nmol/lConclusion: These results suggest that gluteal subcutaneous small resistance arteries of male essential hypertensive patients exhibit a decrement in responsiveness to endothelin-1. The altered design of the hypertensive blood vessels enhanced calculated pressure responses, which may contribute to the maintenance of elevated blood pressure

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