Endothelium-dependent relaxation of canine basilar arteries. Part 1: Difference between acetylcholine- and A23187-induced relaxation and involvement of lipoxygenase metabolite(s).
Vascular responses to acetylcholine (ACh) and the calcium ionophore A23187 were studied in rings of canine basilar arteries. In preparations that were precontracted to a stable plateau by 3 X 10(-6) M prostaglandin F2 alpha (PGF2 alpha), 10(-9) to 10(-7) M A23187 elicited significant relaxation of the basilar arteries if the endothelium was intact. Judging from histologic findings, the ability of a ring to relax in this manner is due to the presence of the endothelium. The same concentration of A23187 did not relax vascular tissues in which the endothelium was purposely disrupted. Although 10(-7) to 10(-3) M ACh did not sufficiently produce endothelium-dependent relaxation of canine basilar artery rings, ACh in the same concentration did produce significant relaxation in canine femoral rings. Our results suggest that the sensitivity of the muscarinic receptor of cerebral arteries appears to be appreciably different from that of peripheral (femoral) arteries. Pretreatment with 1.5 X 10(-5) M indomethacin, a cyclooxygenase inhibitor, potentiated the contractile responses produced by PGF2 alpha in intact rings. Preincubation with the lipoxygenase inhibitors nordihydroguaiaretic acid at (NDGA) at 1.5 X 10(-5) M or AA861 at 10(-5) M prevented A23187-induced relaxation. The same concentration of NDGA and AA861 did not affect endothelium-independent relaxation induced by glyceryl trinitrate. We suggest that endothelium-dependent relaxation of the canine basilar artery by A23187 may be mediated by noncyclooxygenase metabolite(s).
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001488:Basilar Artery / Q000032:analysis / Q000187:drug effects*; D000001:Calcimycin / Q000494:pharmacology*; D004285:Dogs; D004727:Endothelium / Q000502:physiology*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008084:Lipoxygenase / Q000378:metabolism*; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D008855:Microscopy, Electron, Scanning; D009569:Nitric Oxide; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000302:isolation & purification*
D014665:Vasodilator Agents; D009569:Nitric Oxide; D000001:Calcimycin; D009637:Masoprocol; D008084:Lipoxygenase; D000109:Acetylcholine; D007213:Indomethacin