Experimental studies indicate that angiotensin II (ANG II) through its type 1 receptor (AT1) promotes cardiovascular hypertrophy and fibrosis. Therefore, the aim of this study was to analyze whether chronic long-term inhibition of the renin-angiotensin system (RAS) can prevent most of the deleterious effects due to aging in the cardiovascular system of the normal rat. The main objective was to compare two strategies of ANG II blockade: a converting enzyme inhibitor (CEI) and an AT1 receptor blocker (AT1RB). A control group remained untreated; treatment was initiated 2 wk after weaning. A CEI, enalapril (10 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ), or an AT 1RB, losartan (30 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ), was used to inhibit the RAS. Systolic blood pressure, body weight, and water and food intake were recorded over the whole experimental period. Heart, aorta, and mesenteric artery weight as well as histological analysis of cardiovascular structure were performed at 6 and 18 mo. Twenty animals in each of the three experimental groups were allowed to die spontaneously. The results demonstrated a significant protective effect on the function and structure of the cardiovascular system in all treated animals. Changes observed at 18 mo of age in the hearts and aortas were quite significant, but each treatment completely abolished this deterioration. The similarity between the results detected with either enalapril or losartan treatment clearly indicates that most of the effects are exerted through AT 1 receptors. An outstanding finding was the significant and similar prolongation of life span in both groups of treated animals compared with untreated control animals. losartan; enalapril; heart; aorta; life span THE NATURAL PROCESS OF AGING is related to a progressive modification, and ultimately, a loss of organ function. These alterations are common to all species. In general, there is a correlation between the structural and functional changes associated with aging. In mammals, degenerative processes such as arteriosclerosis, the development of senile plaques in the brain, and the replacement of functional parenchyma by fibroconnective tissue in a variety of organs are considered manifestations of aging (19,41).Ultrastructurally, a reduction in the number of cellular organelles such as mitochondria is common in the aging process (13,21,36). Lifelong free radical production could play a main role in the reduction of the number and in both structural and functional mitochondria modifications (6,20,38). It has been widely postulated that reactive oxygen species (ROS) are causally involved in the aging process (19,20). In this sense, earlier data (4, 17) have confirmed that nitric oxide synthase (NOS) activity in the aorta and nitric oxide (NO) production diminish with age, whereas chronic long-term administration of angiotensin II (ANG II) inhibitors maintains endothelial NOS activity in old animals. Moreover, the mitochondria from hearts of aged rats chronically treated with ANG II inhibitors were found to have increased NOS activity and decrease...
