title: Permissive role of NO in alpha 2-adrenoceptor-mediated dilations in rat cerebral arteries.
abstract: Dilations produced with UK-14304, a selective alpha 2-adrenoceptor agonist, in rat middle cerebral arteries (MCAs) were blocked after removal of the endothelium or inhibition of nitric oxide synthase (NOS). After endothelium removal or inhibition of NOS, the addition of subthreshold doses of an exogenous nitric oxide (NO) donor, S-nitroso-N-acetylpenicillamine, restored the dilations produced by UK-14304. In a similar manner the guanosine 3',5'-cyclic monophosphate (cGMP) analogues 8-bromoguanosine 3',5'-cyclic monophosphate and N2,2'-O-dibutyrylguanosine 3',5'-cyclic monophosphate restored the dilations of MCAs after endothelial removal. Because NO cannot be synthesized and released in MCAs after inhibition of NOS, it cannot be directly responsible for the dilation. The basal release of NO from the endothelium acts permissively in the vasodilation by maintaining adequate levels of cGMP. Removal of this basal release of NO by removal of endothelium or inhibition of NOS abolishes the alpha 2-adrenoceptor-mediated dilation.
authors.affiliation: Department of Anesthesiology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Bryan
authors.forename: M L
authors.initials: ML
authors.lastname: Steenberg
authors.forename: M Y
authors.initials: MY
authors.lastname: Eichler
authors.forename: T D
authors.initials: TD
authors.lastname: Johnson
authors.forename: M W
authors.initials: MW
authors.lastname: Swafford
authors.forename: M S
authors.initials: MS
authors.lastname: Suresh
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D000068438:Brimonidine Tartrate; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*
chemical_list: D000316:Adrenergic alpha-Agonists; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D009569:Nitric Oxide; D000068438:Brimonidine Tartrate