DOMINANT CONTRIBUTION OF 5-HYDROXYTRYPTAMTNE OVER THROMBOXANE A2 IN CONTRACTILE RESPONSE OF RABBIT ISOLATED AORTIC PREPARATION TO THROMBIN-ACTIVATED PLATELETS

Activated platelets release two potent vasoconstrictors: viz., 5-hydro xytryptamine (5-HT) and thromboxane A(2) (TXA(2)). The aim of the pres ent study is to clearify which of these vasocontrictors released from activated platelets acts more predominantly on the vascular smooth mus cle. The increase of intraluminal pressure, which is due to the vascul ar smooth muscle contraction, of isolated rabbit aortic preparation in response to 5-HT or STA(2), a stable analog of TXA(2) was significant ly greater when these drugs applied from the intimal surface than when applied from adventitial surface. The contractile response to 5-HT or TXA(2) was markedly depressed by the treatment with methysergide, a 5 -HT receptor antagonist or ONO 3708, a TXA(2) receptor antagonist, res pectively. Thrombin administered from intimal or adventitial surface h ad almost no effect. However, thrombin administered from intimal or ad ventitial surface in the presence of washed platelets produced a marke d contraction. The contractile response to thrombin in the presence of washed platelets was almost unaffected by the treatment with ONO 3708 , while it was completely depressed by the treatment with methysergide . These findings may indicate that 5-HT released from activated platel ets by thrombin contributes more dominantly to the contractile respons e of the vascular smooth muscle than TXA(2).