Mechanisms of whole blood-induced cerebral arterial contraction.
Using rabbit cerebral arteries in an in vitro chamber, we examined the cerebral arterial contraction initiated by clotting whole blood. By using methysergide maleate and a novel thromboxane synthetase inhibitor, 1-carboxyheptylimidazole (1-CHI), we studied the contributions of both serotonin and the prostaglandin metabolite thromboxane A2. Nontreated platelet-rich plasma (PRP) in the presence of methysergide produced a reliable contraction, whereas platelet-poor plasma did not. PRP from a rabbit pretreated with 1-CHI (50 mg/kg) compared to nontreated PRP caused a significantly smaller contraction. Blockade of this cerebral arterial contraction occurred without the disruption of platelet aggregation. Whole blood (1 ml) plus thrombin produced a consistent contraction over the 1 hour that was monitored. Whole blood drawn from a rabbit pretreated with 1-CHI (50 mg/kg) produced a smaller contraction, which began to dissipate in 5 minutes. When nontreated whole blood was added to the chamber in the presence of methysergide maleate (1.3 X 10(-5) g/ml), a contraction less than control was produced, and it persisted at 30 minutes. When whole blood pretreated with 1-CHI (50 mg/kg) was added to the chamber containing methysergide, there was a transient contraction that dissipated to nearly zero at 30 minutes. From our results, it is apparent that the thromboxane synthetase inhibitor has a profound effect on the later phase of blood-induced vasoconstriction. In contrast, the serotonin antagonist affected primarily the initial vasoconstriction and left the later phase largely unaltered. The role of thrombin, used to initiate coagulation, was also examined, and it was found to have a minimal direct constrictive effect when in a plasma solution.
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects; D001777:Blood Coagulation; D001792:Blood Platelets / Q000378:metabolism; D003094:Collagen / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D002546:Ischemic Attack, Transient / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D008954:Models, Biological; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013345:Subarachnoid Hemorrhage / Q000150:complications*; D013928:Thromboxane A2 / Q000502:physiology
D007093:Imidazoles; D012702:Serotonin Antagonists; D012701:Serotonin; D013928:Thromboxane A2; C031572:1-carboxyheptylimidazole; D003094:Collagen; D008784:Methysergide