Response of canine cerebral arteries to endothelin-1

The effects of endothelin-1 (10(-10)-10(-7) M) were isometrically recorded in 4 mm cylindrical segments from the middle cerebral artery of dogs. Cumulative application of endothelin-1 produced marked, sustained contraction of arteries in a concentration-dependent-manner, the maximal response being about 2.6 times higher than that achieved with KCl (50 mM). The contraction by endothelin-1 was unaffected either by endothelium removal or by the cyclo-oxygenase inhibitors indomethacin (10(-6) M) and meclofenamate (10(-6) M). In a Ca(2+)-low (25 microM) solution the endothelin-1-induced arterial contraction was decreased. Therefore, the cerebral vasoconstriction induced by endothelin-1 could be caused by activation of specific receptors located on smooth muscle cells which would lead to the influx of extracellular calcium and vascular musculature contraction.