title: Endothelial L-arginine pathway and regional cerebral arterial reactivity to vasopressin.
abstract: Experiments were designed to characterize the mechanism of vasopressin action in small arteries of brain stem and cerebrum and to determine the role of L-arginine pathway in reactivity of these vessels to vasopressin. Secondary branches of canine basilar arteries (425 +/- 63 microns ID, n = 6) and middle cerebral arteries (466 +/- 30 microns ID, n = 6) were dissected and mounted on glass microcannulas in organ chambers. Changes in intraluminal diameter of the pressurized arteries were measured using a video dimension analyzer. Vasopressin caused endothelium-dependent relaxation in the brain stem arteries [-log half-maximal effective concentration (EC50) = 9.2 +/- 0.4, n = 5] but not in the branches of middle cerebral arteries. In contrast, bradykinin caused identical endothelium-dependent relaxations in arteries of both regions (-log EC50 = 8.0 +/- 0.2, n = 5, and 7.7 +/- 0.1, n = 4 for brain stem and cerebrum, respectively). Relaxations to vasopressin (but not to bradykinin) were reduced in the presence of V1-vasopressinergic antagonist [1-(beta-mercapto-beta-cyclopentamethylenepropionic acid),2-(O-methyl)tyrosine]arginine vasopressin [d(CH2)5-Tyr(Me)AVP;10(-7) M], pertussin toxin (100 ng/ml), and NG-monomethyl-L-arginine (L-NMMA; 10(-4) M). The inhibitory effect of L-NMMA was prevented by L-arginine (3 x 10(-4) M) but not D-arginine (3 x 10(-4) M). These studies suggest that vasopressin causes endothelium-dependent relaxation in canine brain stem arteries. The effect of the neuropeptide appears to be mediated by activation of endothelial V1-vasopressinergic receptors coupled to nitric oxide synthase. This signal transduction pathway is not functional in endothelial cells of branches of middle cerebral arteries.
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota 55905.
authors.forename: Z S
authors.initials: ZS
authors.lastname: Katusić
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology; D001933:Brain Stem / Q000098:blood supply; D002536:Cerebral Arteries / Q000187:drug effects*; D002560:Cerebrovascular Circulation; D004285:Dogs; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D008297:Male; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014667:Vasopressins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D019323:omega-N-Methylarginine
chemical_list: D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D010566:Virulence Factors, Bordetella; D014667:Vasopressins; D001127:Arginine Vasopressin; D019323:omega-N-Methylarginine; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D001120:Arginine