Protective effect of the inhibition of the renin-angiotensin system on aging.

Experimental studies indicate that chronic long-term inhibition of the renin-angiotensin system (RAS) can prevent most of the deleterious effects due to aging in the cardiovascular system and in the kidney of the normal mouse and rat. In this review, all the information available on this subject provided by several studies performed by our research group during the last years is been described. Treatment was initiated either after weaning or at 12 months of age that is about half the normal life span of the rat. A converting enzyme inhibitor: enalapril or an angiotensin II type 1 (AT1) receptor blocker: losartan were used to inhibit the RAS. Cognitive behaviour, emotionality, and locomotor activity were also determined at 10 and 18 months of age in treated since weaning and untreated control rats to elucidate the participation of angiotensin II in memory disfunction. A similar observation was obtained in animals treated from 12 to 18 months of age. Results have demonstrated a significant protective effect on the function and the structure of the cardiovascular system, the kidney and the brain in all the treated animals. Damage observed at 12 months of age was not very significant, but treatment stop further deterioration that was evident in untreated animals. The similarity of the results detected with either enalapril or losartan treatment, clearly indicates that most of the effects are exerted through AT1 receptors. Analysis of the nitric oxide and antioxidant enzymes systems suggest that the protective effect is related to an antioxidant action of the RAS inhibitors and a reduced formation of reactive oxygen species. AngII inhibition might produce changes in the mechanisms of oxidative stress specially at the mitochondrial level. Prevention of mitochondrial decrease and/or damage would be related with the delay of the normal aging process.

Enriched environment, nitric oxide production and synaptic plasticity prevent the aging-dependent impairment of spatial cognition.

In rodents, neuronal plasticity decreases and spatial learning and working memory deficits increase upon aging. Several authors have shown that rats reared in enriched environments have better cognitive performance in association with increased neuronal plasticity than animals reared in standard environments. We hypothesized that enriched environment could preserve animals from the age-associated neurological impairments, mainly through NO-dependent mechanisms of induction of neuronal plasticity. We present evidence that 27 months old rats from an enriched environment show a better performance in spatial working memory than standard reared rats of the same age. Both mtNOS and cytosolic nNOS activities were found significantly increased (73% and 155%, respectively) in female rats from enriched environment as compared with control animals kept in a standard environment. The enzymatic activity of complex I was 80% increased in rats from enriched environment as compared with control rats. We conclude that an extensively enriched environment prevents old rats from the aging-associated impairment of spatial cognition, synaptic plasticity and nitric oxide production.