Aggregating platelets contract isolated canine pulmonary arteries by releasing 5-hydroxytryptamine.
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-46619, produced concentration-dependent contractions of the rings with a maximum averaging 93% of that obtained with KC1. Autologous platelets in concentrations comparable to that in plasma caused contractions averaging 70% of the maximal responses to KC1. Solution withdrawn from baths containing platelet-contracted rings, but not the supernatant from nonaggregated platelets, also caused contraction.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 platelet-induced contractions. Removal of the endothelium did not affect contractile responses to platelets or 5-hydroxy-tryptamine. 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.
D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D004285:Dogs; D004837:Epinephrine / Q000378:metabolism; D066298:In Vitro Techniques; D007650:Ketanserin; D009119:Muscle Contraction; D009638:Norepinephrine / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D010974:Platelet Aggregation; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000097:blood* / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D013929:Thromboxane B2 / Q000097:blood
D010880:Piperidines; D012702:Serotonin Antagonists; D012701:Serotonin; D013929:Thromboxane B2; D007650:Ketanserin; D009638:Norepinephrine; D004837:Epinephrine