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Possible Role of Endothelial Thromboxane A2 in the Resting Tone and Contractile Responses to Acetylcholine and Arachidonic Acid in Canine Cerebral Arteries

Summary The amount of immunoreactive thromboxane B2 (TXB2) released from isolated canine arteries was determined by radioimmunoassay. The amount of TXB2 released from the cerebral, coronary, mesenteric, and saphenous arteries was 47.0 ± 7.2, 4.0 ± 0.6, 4.9 ± 0.5, and 2.7 ± 0.4 pg/mg wet weight tissue/30 min, respectively. The release of TXB2 from the cerebral artery was decreased to <5% by the administration of indomethacin (10-5 M) or OKY-046 (10-4 M), and by intimal rubbing. The release of TXB2 was enhanced nearly twofold by the addition of arachidonic acid (AA) (10-5 M) to the medium, but not by the addition of acetylcholine (ACh) (10-6 M). The cerebral arterial strips maintained the resting tone, which was reduced maximally by papaverine (10-4 M). The resting tone was also reduced dose dependently by a cyclooxygenase inhibitor (indomethacin), a thromboxane A2 (TXA2) synthetase inhibitor (OKY-046), and a TXA2 antagonist (ONO-3708). The resting tone of rubbed strips was about half that of intact strips. ACh and AA induced similar transient contractions in the cerebral artery. Contractions produced by these agents were attenuated by indomethacin (10-7 M), aspirin (5 × 10-5 M), OKY-046 (10-6 M), and ONO-3708 (10-8 M), and abolished by intimal rubbing. From these results, it is concluded that TXA2 is produced in the endothelial cells and may be involved in maintaining the resting tone and contractile response to AA in the canine cerebral artery.