Valsartan abolishes most of the memory-improving effects of intracerebroventricular angiotensin II in rats.
This study explores behavioral effects of angiotensin II (Ang II) and a potent AT(1) receptor inhibitor valsartan ((S)-N-valeryl-N-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]-methyl}-valine). Male Wistar rats (160-180 g) were administered valsartan (10 mg/kg) orally followed, 2 hr later, by Ang II (1 nmol) given intracerebroventricularly (i.c.v., right lateral ventricle). Then 15 min later rats underwent behavioral testing: acquisition of conditioned avoidance responses (CARs), recall of a passive avoidance behavior, open field, elevated "plus" maze, and "chimney" test. Object recognition was tested 60 min after the i.c.v. injections. In addition, effect of valsartan on Ang II stimulated drinking of water was tested. We found that valsartan did not modify the Ang II facilitation of CARs acquisition but abolished the Ang II improvement of memory retrieval and consolidation. The lack of effect of our treatments on the rats' motor activity in the open field makes unspecific contribution of the drug-induced performance changes to the cognitive tests improbable. The anxiogenic action of Ang II, decreased by valsartan, makes an unspecific influence of anxiety possible. The prevention of Ang II increase of drinking by orally given valsartan confirmed effective blockade of the brain AT(1) receptors by the drug.


CONCLUSIONS
valsartan appears to affect cognitive effects of i.c.v. Ang II in rats in a similar way to losartan; anxiolytic activity of valsartan appears to be slightly weaker than that of losartan.
Braszko
Jan J
JJ
Department of Clinical Pharmacology, Medical Academy of Bialystok, Bialystok, Poland. braszko@amb.edu.pl
D000804:Angiotensin II / Q000008:administration & dosage*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects; D004326:Drinking / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000494:pharmacology*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan; D014662:Vasoconstrictor Agents / Q000008:administration & dosage*
D000959:Antihypertensive Agents; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D000068756:Valsartan; D014633:Valine