Endothelins: vasoconstrictor effects and localization in canine cerebral arteries

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Abstract
1 The vascular effects of endothelin and localization of endothelin-like immunoreactivity were characterized in isolated cerebral arteries of dogs. 2 Endothelin-like immunoreactivity was detected in a few populations of endothelial cells of dog basilar artery. 3 Endothelin-1, endothelin-2 and endothelin-3 contracted isolated ring preparations of cerebral arteries in a dose-dependent manner independently of the presence of endothelium. The ED50 values (and 95% confidence intervals) for the contraction were 411 pm (242–697 pm) and 478 pm (295–776 pm) for endothelin-1 and endothelin-2, respectively. Endothelin-3 induced vascular contraction at a higher concentration (ED50 = 26.5 nm, 95% confidence interval = 15.7–45.7 nm). 4 The increases in tone induced by endothelin-1 and endothelin-2 did not return to the resting level after repeated washings, while a rinse with Krebs solution reversed the vasoconstrictor response to endothelin-3. The endothelins did not cause any vasodilator response in arteries precontracted with uridine 5′-triphosphate even in the presence of intact endothelial cells. 5 NiCl2 (1 mm) attenuated the contractions induced by endothelin-3 (10–300 nm) and those to relatively low doses (1 nm) but not higher doses (10–100 nm) of endothelin-1 and endothelin-2. The contractions in response to endothelin-1, endothelin-2 and endothelin-3 were greatly attenuated in Ca2+-free solutions although high concentrations of endothelin-1 and endothelin-2 still evoked contractions. 6 These results suggest that the vasoconstriction induced by endothelin-3 and lower doses of endothelin-1 and endothelin-2, largely depends on the influx of Ca2+ ions. The apparent insensitivity to Ni2+ shows that additional distinct mechanisms also operate in the vasoconstrictor responses to high concentrations of endothelin-1 and endothelin-2. 7 The presence of endothelin-like immunoreactivity in endothelial cells suggests that endothelin is a potential endogenous spasmogen.