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 microm) 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.