Characterization of the effect of endothelins in canine cerebral arteries

In a few populations of endothelial cells of dog basilar arteries, endothelin (ET)-like immunoreactivity was detected to be present. ET-1, ET-2, and ET-3 caused vasoconstrictor responses but not vasodilator responses in isolated ring preparations of dog cerebral arteries in vitro. The ED50 values for the contractions were 411 pM, 478 pM, and 26.5 nM for ET-1, ET-2, and ET-3, respectively. NiCl2 (10(-3) M) attenuated the contractions induced by ET-3 (10(-8)-3 x 10(-7) M) and those to relatively low doses (10(-9) M) but not higher doses (10(-8)-10(-7) M) of ET-1 and ET-2. The contractions in response to ET-1, ET-2, and ET-3 were greatly attenuated in Ca(2+)-free solutions, although high concentrations of ET-1 and ET-2 still evoked contractions. These results suggest that the vasoconstriction induced by ET-3 and lower doses of ET-1 and ET-2 largely depends on the influx of Ca2+ ions. Furthermore, additional distinct mechanisms may contribute to the vasoconstrictor effects of high concentrations of ET-1 and ET-2. The presence of endothelin-like immunoreactivity in endothelial cells suggests that endothelin is a potential endogenous spasmogen.