Protective effect of long-term angiotensin II inhibition

Abstract

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...

Inhibition of Central Angiotensin Converting Enzyme Exerts Anxiolytic Effects by Decreasing Brain Oxidative Stress

“…In this way, experimental data demonstrated that increased reactive oxygen species generation through the activation of NAD(P)H oxidase is an obligatory step in Ang II effects (10,20). It has also been reported that the inhibition of Ang II with specific receptor blockers, but mainly with ACE inhibitors (11), results in decreased oxidative stress status.…”

“…Along these lines, it was demonstrated that mice develop anxious behavior during aging (25), likely due to the accu mulation of reactive oxygen species, which is a characteristic of the aging process in animals. It was also reported that ACE inhibitors reduce anxiety and improve behavioral and motor performance in the aged rat (26) and that the administration of captopril results in a significant prolongation of life span in rats (20). This protective effect could be related to the antioxidant action of RAS inhibitors and a reduced formation of reactive oxygen species.…”

Effects of taxifolin on the activity of angiotensin-converting enzyme and reactive oxygen and nitrogen species in the aorta of aging rats and rats treated with the nitric oxide synthase inhibitor and dexamethasone

“…These data on the ability of taxifolin to bring the ACE activity to the normal level have been obtained for the first time; however, it is possible to compare them with the influence of flavonoids on other manifestations of age-related vessel pathology or pathology caused by the NO synthase inhibitor or glucocorticoid hormones. As known, vessel remodeling in rats enhances with aging (Basso et al 2007) and as a result of the effect of the NO synthase inhibitor (Takemoto et al 1997;Katoh et al 2001). In these cases, pathological changes in vessels are caused by enhanced ACE activity because ACE inhibitors prevent vessel remodeling (Takemoto et al 1997;Katoh et al 2001;Basso et al 2007).…”

“…As known, vessel remodeling in rats enhances with aging (Basso et al 2007) and as a result of the effect of the NO synthase inhibitor (Takemoto et al 1997;Katoh et al 2001). In these cases, pathological changes in vessels are caused by enhanced ACE activity because ACE inhibitors prevent vessel remodeling (Takemoto et al 1997;Katoh et al 2001;Basso et al 2007). Glucocorticoid hormones also increase the ACE activity in the aorta ), blood pressure (Saruta 1996), and the risk of CVD (Nashel 1986;Souverein et al 2004).…”

Differential effects of late-life initiation of low-dose enalapril and losartan on diastolic function in senescent Fischer 344 × Brown Norway male rats

“…Rats treated from weaning through adulthood with the ACE-I, enalapril, or the ARB, losartan, failed to show the expected reduction in myocyte number and increase in cardiac collagen deposition that normally occur during their lifespan (Basso et al 2007). Similarly, treatment with the ACE-I perindopril for 1 year reduced left ventricular mass and interstitial collagen accumulation in both hypertensive and normotensive adult rats (Michel et al 1988).…”