Role of ET A Receptors in the Vasoconstriction Induced by Endothelin-1 in Subcutaneous Small Arteries of Normotensive Subjects and Hypertensive Patients

Abstract

Objective: The aim of our study was to investigate contractile responses to endothelin-1 in the presence or absence of selective blockers of ET A or ET B receptors in subcutaneous small resistance arteries of normotensive subjects and of patients with essential hypertension. Methods: Twenty-four subjects (eight normotensives aged 50 - 4 years, and 16 with essential hypertension aged 53 - 4 years) were included in the study. All subjects were submitted to a biopsy of the subcutaneous fat. Small resistance arteries (internal diameter 160-280 µm) were dissected and mounted on a micromyograph as a ring preparation (Mulvany's technique). The media-to-lumen ratio was calculated. A concentration-response curve to endothelin-1 was then performed in the presence or absence of FR 139317, (a selective blocker of ET A receptors) or of BQ 788, (a selective blocker of ET B receptors). Results: The media-to-lumen ratio was lower in normotensives compared with those subjects with essential hypertension (0.08 - 0.02 vs. 0.12 - 0.05, p < 0.01). The vasoconstriction induced by endothelin-1 was greater in normotensives than in patients with essential hypertension. In normotensives, almost all the vasoconstriction induced by endothelin-1 was blocked by the addition of FR 139317, while in subjects with essential hypertension the effect was smaller. The selective blocker of ET B was devoid of effect in both groups. Conclusions: The vasoconstrictor effect of endothelin-1 in small resistance arteries of normotensive subjects and, in part, also in hypertensive patients is mediated by ET A receptors, while ET B receptors play a minor role, if any. It is, however, possible that a vasoconstrictor effect mediated by ET B receptors located on vascular smooth muscle cells may be masked by the simultaneous stimulation of endothelial ET B receptors which may induce a vasodilation mediated by nitric oxide.