Membrane hyperpolarization is a mechanism of endothelium-dependent cerebral vasodilation.
Acetylcholine (ACh)-induced hyperpolarization of cerebral arteries requires a functional endothelium. The hyperpolarization is reversed by potassium-channel blockers. The goal of this study was to determine whether the hyperpolarization is causally related to endothelium-dependent dilation of isolated cerebral arteries. ACh hyperpolarized rabbit middle cerebral arteries by up to 19 mV. The hyperpolarizations were sustained and did not occur in arteries without endothelial cells or in the presence of potassium-channel inhibitors (3 x 10(-6) M glibenclamide or 5 x 10(-5) M BaCl2). ACh-induced dilator responses were inhibited but not abolished by glibenclamide or BaCl2. Methylene blue also inhibited the dilator responses, and a combination of glibenclamide or BaCl2 and methylene blue greatly diminished the dilation. Nitric oxide relaxed but did not hyperpolarize the vascular smooth muscle cells, and BaCl2 had no effect on the nitric oxide-induced relaxations. These data indicate that the overall cerebral arterial dilator response to ACh is determined by the combined effects of membrane hyperpolarization, which closes voltage-dependent calcium channels, and the actions of a second endothelial factor, probably endothelium-derived relaxing factor.
Brayden
J E
JE
Department of Pharmacology, College of Medicine, University of Vermont, Burlington 05405.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D017609:Barium Compounds; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology; D002560:Cerebrovascular Circulation; D002712:Chlorides; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000502:physiology*; D005905:Glyburide / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008751:Methylene Blue / Q000494:pharmacology; D009994:Osmolar Concentration; D011817:Rabbits; D014664:Vasodilation
D017609:Barium Compounds; D002712:Chlorides; C024986:barium chloride; D001464:Barium; D000109:Acetylcholine; D005905:Glyburide; D008751:Methylene Blue