Platelet-mediated vascular contractions: Inhibition of the serotonergic component by ketanserin

Clerck, Fred De; Nueten, J. M. Van

doi:10.1016/0049-3848(82)90009-3

Cited by 64 publications

(39 citation statements)

References 16 publications

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“…The response produced by platelets is mediated primarily by the release of 5-hydroxytryptamine since serotonergic antagonists reverse the platelet-evoked contractile response. The conclusions of this study agree with previous investigations of plateletinduced contraction of rat caudal artery preparations (27) in which ketanserin, but not cyclooxygenase blockade, markedly inhibited contractions caused by platelets. In the rat caudal artery, however, relaxation by ketanserin of platelet-contracted vessels was not complete and, unlike that observed in the present study, did not parallel precisely the relaxation of vessels contracted with 5-hydroxytryptamine.…”

Section: Discussionsupporting

confidence: 82%

Aggregating platelets contract isolated canine pulmonary arteries by releasing 5-hydroxytryptamine.

McGoon¹,

Vanhoutte²

1984

J. Clin. Invest.

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Abstract. To examine the effect of platelets and 5-hydroxytryptamine on pulmonary arterial smooth muscle, rings of canine pulmonary arteries, with and without endothelium, were studied under isometric conditions in physiological salt solution. 5-Hydroxytryptamine, but not the thromboxane-like endoperoxide analogue U-466 19, produced concentration-dependent contractions of the rings with a maximum averaging 93% of that obtained with KCL. Autologous platelets in concentrations comparable to that in plasma caused contractions averaging 70% of the maximal responses to KCL. Solution withdrawn from baths containing platelet-contracted rings, but not the supernatant from nonaggregated platelets, also caused contraction. The serotonergic antagonists cyproheptadine, ketanserin, and methysergide caused concentration-dependent inhibition and eventually abolition of contractions evoked by platelets and 5-hydroxytryptamine. Phentolamine and prazosin produced significantly less inhibition of the contractile response to platelets. Pretreatment of the platelets with indomethacin or meclofenamate reduced thromboxane release but had no effect on plateletinduced contractions. Removal of the endothelium did not affect contractile responses to platelets or 5-hydroxytryptamine. These experiments demonstrate that in the canine pulmonary artery: (a) 5-hydroxytryptamine is the predominant mediator of the contractile response triggered by platelet aggregation; and (b) unlike in other blood vessels, the endothelium cannot curtail the contractile response to aggregating platelets.A preliminary report of these findings was published in abstract form (1983. Fed. Proc. 42:593). Introduction 5-Hydroxytryptamine (serotonin) contracts canine and human isolated intrapulmonary vascular preparations (1-4) and elevates pulmonary vascular resistance in intact organisms (5-10) or vascularly isolated perfused lungs (1 1-13). Microembolization or in situ aggregation of platelets produces an elevation of pulmonary vascular resistance, leading to pulmonary hypertension, which can be attributed in part to the release of vasoactive substances (5,(14)(15)(16)(17)(18)(19)

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Section: Discussionsupporting

confidence: 82%

Aggregating platelets contract isolated canine pulmonary arteries by releasing 5-hydroxytryptamine.

McGoon¹,

Vanhoutte²

1984

J. Clin. Invest.

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“…Ad ditionally, the monoamine largely amplifies the human platelet aggregation response to various agonists including ADP, epinephrine, norepinephrine and collagen (4, 5, 15) and induces itself strong aggregation of human platelets, pre-sensitized with norepinephrine (15). Recently, De Clerck and Van Nueten (7) reported that ketanserin inhibits the reversible aggregation induced by 5-HT in human platelet-rich plasma; and they reported that after both in vitro and oral administration to man, it also reduces the serotonergic amplification of agonists involving norepine phrine. Thus, there have been many reports concerning a close interaction particularly between norepinephrine and 5-HT in platelet aggregation.…”

Section: Discussionmentioning

confidence: 99%

“…The other effect attributable to SGB-1534 is a 5-HT2 antagonism (2). This drew our attention to the fact that 5-HT plays an important role in platelet aggregation (4, 5) and that ketanserin, a selective antagonist at 5-HT2 receptors (6), effectively inhibits the ag gregation (7).…”

mentioning

confidence: 99%

Effects of a New Antihypertensive Agent, SGB-1534, on Rat Platelet Aggregation

Aono¹,

Sakai²

1986

Japanese Journal of Pharmacology

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“…Isolated blood vessels (from various species including rat, rabbit, dog, human) contract when exposed to platelets that are made to aggregate by contact with the vessel wall or stimulation with thrombin ( Fig. 12) (29,30,46,50,159,166,180,181,269). These aggregating platelets synthesize thromboxane A2 and release serotonin.…”

Section: Platelet-vessel Wall Interactionmentioning

confidence: 99%

“…Subthreshold or threshold concentrations of serotonin potentiate (amplify) contractions of blood vessels induced by other vasoconstrictor agonists, including angiotensin 11, histamine, norepinephrine (whether exogenously added or released from sympathetic nerves), degradation products of fibrin and fibrinogen, prostaglandin FZu, thromboxane A2, and the thromboxane A2 mimetic U 44069 (46,64,89,142,164,172,182,234,265,266,(268)(269)(270). This amplifying effect of serotonin on responsiveness to other vasoactive agents also occurs in vivo in sheep and man (184,226).…”

Section: Amplifying Effects Of Serotoninmentioning

confidence: 99%