Participation of arginine vasopressin-mediated and adrenergic system-mediated mechanisms in the hypertension induced by intracerebroventricular administration of NMDA in freely moving rats.
Effects of intracerebroventricular (third ventricle) injection of N-methyl-D-aspartate (NMDA) on arterial blood pressure, on heart rate, on arginine vasopressin (AVP) and levels of catecholamines in plasma and on the behaviour of normotensive freely-moving rats have been evaluated. N-Methyl-D-aspartate significantly (P less than 0.01) increased arterial blood pressure and levels of catecholamines and AVP in plasma. With 0.1-1.0 micrograms/rat all animals presented psychomotor agitation, stereotyped movements, hyperexcitability, exophthalmus, dyspnoea, jumping, rearing and teething. The selective antagonist for NMDA receptors, 2-APV injected in the third ventricle, significantly (P less than 0.01) antagonized the hypertension, the increase in levels of catecholamines and AVP in plasma and behavioural effects. An antagonist of alpha 1 adrenergic receptors, prazosin (i.v.), an agonist of alpha 2 adrenergic receptors, clonidine (i.c.v.) and a relatively selective antagonist of V1 subtype of receptor of AVP, CGP 25838 (i.c.v. and i.v.), 15 min before NMDA, significantly (P less than 0.01) decreased the effects induced by the injections of NMDA. On the contrary, an antagonist of opiate receptors, naloxone (i.v.), 15 min before NMDA, significantly (P less than 0.01) increased the NMDA-induced modifications. Pretreatment with the antagonists at these doses, did not significantly modify the basal values of arterial blood pressure and behaviour. Only 2-APV sometimes induced ataxia, lasting about 5 min. This study points out an increase in the central sympathetic efferent activity and in release of AVP involved in the NMDA-induced cardiovascular and behavioural effects.
Institute of Pharmacology and Toxicology, 1st Faculty of Medicine and Surgery, University of Naples Federico II, Italy.
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D015763:2-Amino-5-phosphonovalerate / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000097:blood*; D006339:Heart Rate / Q000187:drug effects*; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000494:pharmacology*; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood*; D011224:Prazosin / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D001127:Arginine Vasopressin; D009270:Naloxone; D016202:N-Methylaspartate; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; D015763:2-Amino-5-phosphonovalerate; D003000:Clonidine; D009638:Norepinephrine; D011224:Prazosin; D004837:Epinephrine