title: Central inhibition of nitric oxide synthesis increases blood pressure and heart rate in anesthetized rats.
abstract: In the present study we evaluated the cardiovascular responses to inhibition of endogenous nitric oxide (NO) formation in the brain with intracerebroventricular (i.c.v) administration of N omega-nitro-L-arginine methyl ester (L-NAME), a specific inhibitor of NO synthase. L-NAME (30 micrograms and 300 micrograms i.c.v) induced a dose-dependent increase in mean arterial pressure and heart rate in anesthetized normotensive rats, while its enantiomer D-NAME (300 micrograms i.c.v.) increased blood pressure only slightly and transiently. The pressor response to L-NAME was partially attenuated by i.c.v. administration of NO precursor L-arginine (300 micrograms), whereas D-arginine, the stereoisomer which cannot serve as a percursor for the biosynthesis of NO, was ineffective. Inhibition of beta 1-adrenoceptors by pretreatment with atenolol (2.5 mg/kg i.v.) reduced the pressor and tachycardic effect of subsequently administered L-NAME, whereas muscarinic receptor antagonist methylatropine (2 mg/kg i.v.) did not affect the cardiovascular effects of L-NAME. These findings imply that the pressor response to i.c.v. L-NAME results from withdrawal of the inhibitory effect of endogenous NO on a central pressor mechanism which acts by increasing sympathetic outflow.
authors.affiliation: Department of Pharmacology and Toxicology, University of Helsinki, Finland.
authors.forename: M L
authors.initials: ML
authors.lastname: Nurminen
authors.forename: A
authors.initials: A
authors.lastname: Ylikorkala
authors.forename: H
authors.initials: H
authors.lastname: Vapaatalo
mesh_terms: D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004791:Enzyme Inhibitors; D019331:NG-Nitroarginine Methyl Ester