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

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. [ABSTRACT FROM AUTHOR]