NONPEPTIDE ANGIOTENSIN-II RECEPTOR ANTAGONIST AND ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR - EFFECT ON A RENIN-INDUCED DEFICIT OF A PASSIVE-AVOIDANCE RESPONSE IN RATS

Non-peptide receptor ligands with differential affinity for the angiotensin II-1 (AII-1) receptor (EXP3312, EXP3880) or the AII-2 receptor (PD123177) and an angiotensin converting enzyme (ACE) inhibitor captopril were evaluated for the ability to protect against a renin-induced performance deficit in a passive avoidance (PA) task in rats. The ability to retain a PA response was shown to decrease as the dose of intracerebroventricularly (i.c.v.) administered renin increased with maximal retention deficits occurring at 1.0-mu-g/5-mu-l i.c.v. EXP3312 (1-100 mu-g/5-mu-l i.c.v.) and EXP3880 (1-100-mu-g/5-mu-l i.c.v.) produced dose-dependent increases in retention latencies when co-administered with renin. The peak effect dose (PED) for EXP3312 and EXP3880 was 3 and 30-mu-g i.c.v., respectively. In contrast, PD123177 was not effective in preventing the renin-induced decrease in retention across a broad range of doses (0.1-100-mu-g/5-mu-l i.c.v.). Captopril (1-100-mu-g/5-mu-l i.c.v.) also prevented the renin-induced performance deficit with a PED of 30-mu-g/5-mu-l i.c.v. These results suggest that renin given i.c.v. produces a deficit in performance of a PA response in rats and that this effect can be attenuated by an ACE inhibitor, AII-1 receptor ligands, but not AII-2 receptor blocker.