Age-related decline in spatial learning and memory: attenuation by captopril.

Spontaneously hypertensive rats (SHR) compared to normotensive rats display an accelerated decline in spatial learning and memory. However, few studies have systematically examined the independent contribution of hypertension vs. other age-related mechanisms to this decline. The present study uses a repeated acquisition water maze task to test the hypothesis that hypertension and/or the presence of angiotensin II can accelerate the age-related decrease of spatial learning and memory in rats. We have previously shown that both SHR and Wistar-Kyoto rats (WKY) display age-related decreases in spatial learning and memory; however, the rate of decline differs between the strains. The present results demonstrate that compared to young rats of the same strain, learning and memory in SHR declines significantly already at 12 months of age, and at 24 months of age both SHR and WKY rats are severely impaired in the water maze task. Lifetime treatment of either SHR or WKY with the antihypertensive drug captopril [an angiotensin converting enzyme (ACE) inhibitor] significantly attenuates the age-related impairment in learning and memory. In contrast, chronic treatment of SHR with captopril from 6 months of age only modestly decreases the decline in learning and memory. Whereas lifetime treatment with the vasodilator drug hydralazine also reduces arterial pressure in SHR, this treatment does not significantly preserve learning in 24-month-old SHR. Together, the data suggest captopril can delay the decline in spatial learning and memory in both aging SHR and WKY. Further, the results indicate that the memory enhancing effects of captopril are not primarily the due to the ability of captopril to lower blood pressure.