Platelets enhance anoxic contraction of rat aortic rings through platelet-activating factor-dependent mechanism.

Previous studies indicate that anoxia results in vascular smooth muscle contraction, and this phenomenon is mediated in part by a decrease in release of endothelium-derived relaxing factor (EDRF). The role of platelets that relax blood vessels by eliciting EDRF release on anoxic contraction is not known. To examine anoxic contraction in the presence of platelets, we exposed norepinephrine (NE)-precontracted rat aortic rings to washed platelets and then induced anoxia (switch from 95% O2 to 95% N2). Platelets transiently relaxed the precontracted aortic rings (decrease in tension 49 +/- 4%, n = 18). The subsequent anoxia-induced contraction was augmented, however (magnitude of contraction 71 +/- 12 vs. 49 +/- 6% in parallel buffer-treated rings, n = 18, p < 0.01). To determine the mechanism of platelet-mediated augmentation of anoxic contraction, vascular rings were treated with indomethacin, the thromboxane A2 (TxA2)/endoperoxide receptor antagonist SQ29,548, lipoxygenase inhibitor U60,257B, free oxygen radical scavengers superoxide dismutase (SOD) plus catalase, serotonin (S2) receptor blocker LY53,857, or the ADP scavenger apyrase. Although apyrase, U60,257B, SQ29,548, LY53,857, and SOD plus catalase had no effect on augmentation of anoxic contraction in the presence of platelets, treatment with indomethacin markedly decreased (p < 0.02) the augmented anoxic vasoconstriction. Because indomethacin decreases the activity of platelet-activating factor (PAF), vascular rings were treated with two different specific PAF receptor antagonists: L-659,989 and WEB 2170 BS. Both these agents blocked the platelet-augmented anoxic vasoconstriction. In addition, synthetic PAF (10(-7) and 10(-6) M) in itself potentiated anoxic contraction, mimicking the activity of platelets.(ABSTRACT TRUNCATED AT 250 WORDS)