title: Vasodilation of brain surface arterioles by blockade of Na-H+ antiport and its inhibition by inhibitors of KATP channel openers.
abstract: Pial artrioles of rats were monitored in vivo and found to dilate in dose-dependent fashion upon application of either benzamil or ethyl isopropyl amiloride, both of which are inhibitors of the sodium-hydrogen antiport. Antiport blockade is known to decrease the internal pH of vascular smooth muscle (VSM). The dilation was blocked by 1 microm glibenclamide, which in that dose is a selective inhibitor of ATP sensitive potassium channels (K(ATP)). The nitric oxide synthase inhibitor nitro-l arginine (l-NNA) also blocked the response. Previous studies of this preparation under the same experimental conditions showed that l-NNA inhibited dilation by K(ATP) openers and that nitric oxide had no permissive action in this setting. Moreover, one study by others has demonstrated a pH sensitive site on the internal surface of K(ATP) while another study by others has demonstrated that sodium propionate, a direct acidifier of the cell, dilates rat basilar artery in K(ATP)-dependent fashion. Therefore, the present data support the following conclusions: decrease of internal pH dilates brain arterioles; the response is K(ATP) dependent; in some situations, inhibitors of nitric oxide synthase can inhibit K(ATP) and K(ATP)-dependent dilations including those produced by decrease of internal pH.
authors.affiliation: Department of Pathology (Neuropathology), Virginia Commonwealth University Medical Center-Medical College of Virginia Campus, Richmond VA 23298-0017, USA. Wirosenb@aol.com
authors.forename: William I
authors.initials: WI
authors.lastname: Rosenblum
authors.forename: Enoch P
authors.initials: EP
authors.lastname: Wei
authors.forename: Hermes A
authors.initials: HA
authors.lastname: Kontos
mesh_terms: D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D008297:Male; D010841:Pia Mater / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D026902:Potassium Channel Blockers; D015221:Potassium Channels; D017923:Sodium-Hydrogen Exchangers; C013407:benzamil; D000584:Amiloride; D005905:Glyburide