An endothelium-dependent contraction induced by A-23187, a Ca++ ionophore in canine basilar artery

In most isolated canine basilar arteries tested, Ca++ ionophore A-23187 induced a small relaxation followed by a transient contraction. Both contraction and relaxation were abolished by removal of endothelium. The endothelium-dependent contraction induced by A-23187 was attenuated by a phospholipase A2 inhibitor (quinacrine), cyclooxygenase inhibitors (aspirin and indomethacin), a thromboxane A2 (TXA2) synthetase inhibitor (OKY-046) and a TXA2 antagonist (ONO-3708). The A-23187-induced contraction was abolished by lowering the Ca++ concentration of medium to 10%, whereas the contraction induced by 9,11-epithio-11,12-methano-TXA2 (STA2) was attenuated slightly by lowering [Ca++]. The A-23187-induced contraction was reduced markedly by nifedipine (10(-9) to 10(-7) M), but the STA2-induced contraction was only attenuated slightly by nifedipine. Bay K 8644 did not affect the A-23187- and STA2-induced contractions. The present experiments demonstrate that A-23187 induced an endothelium-dependent contraction in canine basilar artery, and suggest that Ca++ might play a key role in production of an endothelium-derived contracting factor (probably TXA2).