Angiotensin-Converting Enzyme Inhibition, Body Composition, and Physical Performance in Aged Rats

Carter, Christy S.; Cesari, Matteo; Ambrosius, Walter T.; Hu, Nan; Diz, Debra I.; Oden, Sherry; Sonntag, William E.; Pahor, Marco

doi:10.1093/gerona/59.5.b416

Cited by 67 publications

(73 citation statements)

References 40 publications

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“…34 Treatment of these rats for 6 months with an ACE inhibitor or AT 1 receptor blocker beginning at 24 months of age decreased fat mass without lowering blood pressure. 35 However, RAS blockade does not lower insulin or leptin relative to older control rats and does not alter the excretion of Ang II or protein. Thus, a different pattern of protein and Ang II excretion is evident in healthy aging as opposed to Fischer 344 rats, although neither rat exhibits elevated SBP as part of the aging process.…”

Section: Intrarenal Ras Regulation In Animals Without Age-related Hypmentioning

confidence: 94%

Lewis K. Dahl Memorial Lecture

Diz

2008

Hypertension

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identified many of the relationships that underlie our current thinking and focus of research on hypertension. Among the first to establish the interactions between salt and hypertension, the realization that genetic factors played a major role in how the kidney responded to salt loads 1 led to development of the genetically predisposed Dahl salt-sensitive rat. His research, although not specifically directed toward aging, recognized that the effects of high-salt diets were not necessarily immediate. In fact, he suggested that at least one third of the life span was required for salt-induced changes in systolic blood pressure (SBP).I am very grateful for the honor of presenting the Dahl lectureship on work, which, over the past several years, has had aging as the focus. The emphasis has been on the autonomic nervous system, as influenced by the renin-angiotensin system (RAS), specifically, the balance between angiotensin (Ang) II and Ang-(1-7) and the contributions of brain cardiovascular areas to the constellation of changes occurring with advancing age. The overall message derived is that, although the brain RAS plays a major role in all of the age-related changes in cardiovascular and metabolic function, neither the SBP nor the metabolic changes appear to be initiating factors in the activation of the intrarenal RAS or the decline in kidney function during aging ( Figure 1). Differential Regulation of the Circulating and Intrarenal RAS During AgingComponents of the classical circulating RAS, in particular, renin release from the juxtaglomerular cells of the kidney, undergo a decline in older animals. This includes reductions in renal tissue renin mRNA, juxtaglomerular cell renin content, responsiveness of renin release to various challenges, and plasma renin and angiotensin (Ang) II. [2][3][4][5][6][7][8][9] The renal vasoconstrictor responses to exogenously administered Ang II are increased in older animals, 6 perhaps resulting from the reductions in the circulating system. In striking contrast, however, kidney Ang II content increases in older animals. 6This latter finding is not surprising, because all of the components of the RAS are synthesized locally within the kidney, 10 -12 and local production of Ang peptides is regulated independent of the circulating system. 11,13-16 Thus, whereas the juxtaglomerular cell renin and its release into the circulation are considered representative of the circulating/hormonal RAS, renal tissue content, tubular fluid, or urinary RAS components are considered representative of the intrarenal RAS.The concept of differential regulation of the circulating and intrarenal or other tissue RAS is not new.12 One possibility for these differences relate to the increase in SBP. An increase in arterial pressure during aging may lead to a baromediated reduction in renin release from the kidney, contributing to the decline in the circulating RAS. In contrast, for the intrarenal system, there is evidence that the regulation of tubular renin may be opposite to or at least different fro...

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Section: Intrarenal Ras Regulation In Animals Without Age-related Hypmentioning

confidence: 94%

Lewis K. Dahl Memorial Lecture

Diz

2008

Hypertension

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“…Forelimb grip strength was determined using an automated grip strength meter (Columbus Instruments, Columbus, OH) as previously described [5]. The mean force (grams) was calculated over three trials and was divided by body weight.…”

Section: Grip Strengthmentioning

confidence: 99%

Comparison of lifelong and late life exercise on oxidative stress in the cerebellum

Cui

Hofer

Rani

et al. 2009

Neurobiology of Aging

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Aging was associated with increased oxidation of DNA, RNA, and lipids in the cerebellum of male rats. DNA and lipid oxidation was reduced by lifelong (94 weeks) voluntary exercise on a running wheel. A reduction in cerebellar lipid oxidation, but not RNA or DNA oxidation, was observed following 3 months of moderate exercise or dietary supplementation of vitamin E, initiated at 18 months of age. The level of lipid oxidation correlated with measures of forelimb grip strength. The results indicate that lifelong exercise attenuates multiple molecular markers of age-related oxidative damage in the cerebellum. In addition, modest exercise initiated late in life can have a beneficial effect on lipid oxidation and motor function.

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“…In contrast, a study with older rats (24 months old) reported smaller reductions in body fat composition and treatment of 24 weeks was much longer. 43 When considering these studies, it seems likely that the effect of ACE inhibition on body weight and appetite may be influence by age, with younger animals being more sensitive to the treatments and reducing appetite as well as body fat mass in a shorter treatment period. There may also be a dose-related effect on appetite, as the dose used in this study (1.2 mg kg À1 per day)…”

Section: Mechanisms Underlying the Reduction In Fat Massmentioning

confidence: 99%

Selective reduction in body fat mass and plasma leptin induced by angiotensin-converting enzyme inhibition in rats

et al. 2008

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Objective: There is emerging evidence that angiotensin stimulates adipocyte differentiation and lipogenesis. This study tested the hypothesis that inhibition of angiotensin II by treatment with an angiotensin-converting enzyme inhibitor, perindopril, would reduce fat mass in rats. Design: After a 12-day baseline, rats were divided into two groups: one was untreated and the other received perindopril (1.2 mg kg À1 per day) in drinking water for 26 days. Subjects: In total, 16 male Sprague-Dawley rats aged 10 weeks at the start of the study. Measurements: Plasma leptin was measured in samples collected at baseline, half-way through and at the end of treatment. Body weight, food and water intake were measured daily throughout the experiment. Body fat mass, bone and lean mass were determined by dual energy X-ray absorptiometry (DEXA) at the end of the treatment period. Results: Daily food intake was the same in both groups throughout the study. By the end of treatment, animals receiving perindopril showed a modest reduction in weight gain relative to the untreated animals (62.4 ± 5.0 g vs 73.0 ± 4.0 g; Po0.05). DEXA analysis showed that body composition was greatly altered and the perindopril-treated group had 26% less body fat mass than the untreated group (61.0 ± 5.2 g vs 44.4 ± 4.2 g; Po0.01). The reduction in body fat mass was correlated with reductions in the weight of both the epididymal and retroperitoneal fat pads (Po0.001). Similarly, plasma leptin was reduced by perindopril treatment (4.64 ± 0.56 ng ml À1 ) compared to the untreated group (8.27 ± 1.03 ng ml À1 ; Po0.001). In contrast, there were no differences in lean or bone mass between the two groups. Conclusion: Oral treatment with perindopril selectively reduced body fat mass without influencing daily food intake. In contrast, there were no differences in lean or bone mass between the two groups.

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Angiotensin-Converting Enzyme Inhibition, Body Composition, and Physical Performance in Aged Rats

Cited by 67 publications

References 40 publications

Lewis K. Dahl Memorial Lecture

Lewis K. Dahl Memorial Lecture

Comparison of lifelong and late life exercise on oxidative stress in the cerebellum

Selective reduction in body fat mass and plasma leptin induced by angiotensin-converting enzyme inhibition in rats

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