Objective: Endothelin-A-receptor-antagonists inhibit angiotensin II- and noradrenaline-induced vasoconstriction. Whether functional constrictive endothelin-B-receptors play a role in the endothelin-1-mediated potentiation of vasoconstriction to angiotensin II and noradrenaline is thus far unknown.
Methods: We studied the effects of noradrenaline and angiotensin II (10 mol/l) in the presence of exogenous endothelin-1 (10 mol/l) with and without selective endothelin-B-receptor-blockade by BQ-788 (10 mol/l) and dual receptor blockade with BQ-788 and the endothelin-A-selective antagonist BQ-123 (10 mol/l) in 14 healthy male volunteers (aged 20-28). Studies were performed in the human skin microcirculation under in vivo conditions using laser-Doppler flowmetry and double injection technique. The area under the time-response curve of all doses was calculated.
Results: Endothelin-1 potentiated the effects of angiotensin II and noradrenaline (-944 +/- 139 perfusion units (PU), P < 0.01; -926 +/- 117 PU, P < 0.05, respectively). In the presence of BQ-788, the potentiating effect of endothelin-1 was significantly blunted (-624 +/- 132 PU, P < 0.01; -549 +/- 136 PU, P < 0.01, respectively). In the presence of BQ-123 and BQ-788 the vasoconstriction was fully inhibited (431 +/- 108 PU, P < 0.001 and 421 +/- 86 PU, P < 0.001, respectively).
Conclusions: These data suggest that functional vasoconstrictive endothelin-B receptors on vascular smooth muscle cells may contribute to the potentiating effects of high local concentrations of endothelin-1 on the vasoconstriction to noradrenaline and angiotensin II in human microcirculation.