Susceptibility to provoked cerebral infarction is not increased in a rat model of pharmacologically-induced hypertension despite endothelial dysfunction

Fundam Clin Pharmacol. 2000 May-Jun;14(3):177-86. doi: 10.1111/j.1472-8206.2000.tb00014.x.

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.

MeSH terms

  • Animals
  • Aorta, Thoracic / pathology
  • Aorta, Thoracic / physiopathology
  • Cerebral Infarction / etiology*
  • Cerebral Infarction / pathology
  • Cerebral Infarction / physiopathology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / physiopathology*
  • Enzyme Inhibitors / pharmacology
  • Hypertension / chemically induced
  • Hypertension / complications
  • Hypertension / enzymology
  • Hypertension / physiopathology*
  • Male
  • Middle Cerebral Artery / pathology
  • Middle Cerebral Artery / physiopathology
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Rats
  • Rats, Wistar
  • Vasodilation / physiology*

Substances

  • Enzyme Inhibitors
  • Nitric Oxide Synthase
  • NG-Nitroarginine Methyl Ester