Vasoconstrictive responses elicited by endothelin in bovine cerebral arteries

1. Endothelin (ET-1) induced concentration-dependent contractions, which were slowly developed in segments of bovine cerebral arteries. Furthermore, this agent produced tachyphylaxis. 2. The contractions evoked by ET-1 were markedly reduced in Ca-free medium containing 1 mM EGTA and by the Ca channel antagonist, nifedipine (1 microM), but increased by the Ca channel agonist, BAY K 8644 (10 nM). 3. The contractions caused by ET-1 were significantly reduced by the protein kinase C (PKC) inhibitor, staurosporine (1 and 10 nM). 4. These results indicate that ET-1 induced potent vasoconstrictive responses, probably mediated by PKC activation, which were mainly dependent on extracellular Ca; this Ca enters the smooth muscle cells via dihydropyridine sensitive Ca channels.