title: Susceptibility to provoked cerebral infarction is not increased in a rat model of pharmacologically-induced hypertension despite endothelial dysfunction.
abstract: An increase in susceptibility to provoked stroke has been described in a genetically-determined rat model of hypertension. We investigated whether the susceptibility to provoked cerebral ischaemia was also increased in a rat model of pharmacologically-induced hypertension with endothelial dysfunction. Chronic inhibition of nitric oxide synthase induced by N(omega)-nitro-L-arginine methyl ester (L-NAME) administration (50 or 75 mg.kg(-1) x day(-1)) in drinking water for 6 weeks caused a sustained hypertension, comparable in the two groups. Endothelium-dependent relaxation induced by acetylcholine or A23187 was significantly, and dose-dependently, impaired in rats receiving L-NAME, as proven by a decrease in maximal relaxation and increase of EC50, as compared to control. Endothelium-independent relaxation induced by sodium nitroprusside was not different in the three groups. Aortic media area was significantly, and dose-dependently, increased following chronic nitric oxide inhibition. Cerebral infarct volumes were not increased in L-NAME-treated groups independently of the level of endothelial dysfunction induced by chronic L-NAME administration. These data demonstrate that susceptibility to cerebral infarction was not increased in a non-genetically determined hypertension model in spite of the development of endothelial dysfunction and vascular structure alterations.
authors.affiliation: Laboratoire de pharmacologie, faculté de médecine, 1, place de Verdun, 59045 Lille, France. r-bordet@chru-lille.fr
authors.forename: R
authors.initials: R
authors.lastname: Bordet
authors.forename: Q
authors.initials: Q
authors.lastname: Pu
authors.forename: F
authors.initials: F
authors.lastname: Puisieux
authors.forename: D
authors.initials: D
authors.lastname: Deplanque
authors.forename: O
authors.initials: O
authors.lastname: Jaboureck
authors.forename: D
authors.initials: D
authors.lastname: Leys
authors.forename: B
authors.initials: B
authors.lastname: Vallet
authors.forename: B
authors.initials: B
authors.lastname: Dupuis
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology / Q000503:physiopathology; D002544:Cerebral Infarction / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000150:complications / Q000201:enzymology / Q000503:physiopathology*; D008297:Male; D020768:Middle Cerebral Artery / Q000473:pathology / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester