Dominant contribution of 5-hydroxytryptamine over thromboxane A2 in contractile response of rabbit isolated aortic preparation to thrombin activated platelets.
Activated platelets release two potent vasoconstrictors: viz., 5-hydroxytryptamine (5-HT) and thromboxane A2 (TXA2). The aim of the present study is to clarify which of these vasoconstrictors released from activated platelets acts more predominantly on the vascular smooth muscle. The increase of intraluminal pressure, which is due to the vascular smooth muscle contraction, of isolated rabbit aortic preparation in response to 5-HT or STA2, a stable analog of TXA2 was significantly greater when these drugs applied from the intimal surface than when applied from adventitial surface. The contractile response to 5-HT or TXA2 was markedly depressed by the treatment with methysergide, a 5-HT receptor antagonist or ONO 3708, a TXA2 receptor antagonist, respectively. Thrombin administered from intimal or adventitial surface had almost no effect. However, thrombin administered from intimal or adventitial surface in the presence of washed platelets produced a marked 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 platelets by thrombin contributes more dominantly to the contractile response of the vascular smooth muscle than TXA2.
Nakanishi
H
H
Department of Pharmacology, Fukushima Medical College, Japan.
Matsuoka
I
I
Ono
T
T
Nakahata
N
N
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D017482:Receptors, Thromboxane; D012702:Serotonin Antagonists; D014662:Vasoconstrictor Agents; D012701:Serotonin; D013928:Thromboxane A2; C037866:STA 2; C049855:ONO 3708; D013917:Thrombin; D009638:Norepinephrine; D007213:Indomethacin; D008784:Methysergide