Vasoconstrictor mechanism of neuropeptides augmented after endothelial removal in isolated, perfused canine basilar arteries.
In order to investigate the functional role of endothelium and vasoeffector mechanism in cerebrovascular responses to neuropeptides, the stainless steel cannula inserting method was applied to examine the responses to intraluminally-applied bradykinin, substance P and vasopressin in isolated and perfused canine basilar arteries. In control vessels with intact endothelium, each neuropeptide induced a monophasic dilation at lower doses, and a biphasic response, i.e., an initial dilation followed by a secondary constriction, at higher doses. The dilation was significantly reduced and the constriction was significantly enhanced, while the dilation to papaverine was not modified by endothelial removal with intraluminal saponin. The same tendency was observed in the responses after extraluminal treatment with oxyhaemoglobin. The monophasic constrictions to prostaglandin F2 alpha and potassium chloride were significantly potentiated by the endothelial removal. The augmented constrictions to the neuropeptides were significantly diminished by indomethacin (a cyclooxygenase inhibitor), OKY-046 (a thromboxane synthetase inhibitor) and nimodipine (a dihydropyridine calcium antagonist), but not by AA-861 (a lipoxygenase inhibitor). These results suggest that the neuropeptide causes an endothelium-dependent dilation and a constriction of smooth muscles, and that the enhanced constriction might be relevant in part with thromboxane A2, linked with calcium influx into smooth muscle cells in cerebral arteries.
Tsuji
T
T
Department of Neurosurgery, Shinshu University School of Medicine, Matsumoto, Japan.
Cook
D A
DA
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects* / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D013373:Substance P / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*; D014667:Vasopressins / Q000494:pharmacology*
D014667:Vasopressins; D013373:Substance P; D001920:Bradykinin; D007213:Indomethacin