Vasoconstrictor actions of endothelin-1 in human resistance vessels

The contractile response to endothelin-1 was studied in isolated human resistance vessels in the presence and absence of extracellular calcium. Endothelin-1 was 1000-fold more potent than noradrenaline, with an ED50 of 6.5 +/- 1.26 x 10(-9) mol/l compared with 2.1 +/- 0.7 x 10(-6) mol/l. Calcium depletion by repeated stimulation with noradrenaline in a calcium-free medium attenuated but did not prevent a sustained contraction in response to endothelin-1 (30% of control). On re-adding calcium to the bath a full contraction immediately occurred. These experiments suggest that an endothelin-1-induced contraction is largely dependent on the presence of extracellular calcium, but a partial contraction can be induced in a calcium-free medium and this may be dependent on mobilization of intracellular calcium from a store not affected by repeated noradrenaline stimulation.