Effects of renin–angiotensin system blockade in the aging kidney

Ferder, León; Inserra, Felipe; Basso, Nidia

doi:10.1016/s0531-5565(02)00264-4

Cited by 45 publications

(39 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…40,41 With systemic treatments, improvements in metabolism and renal function may involve actions at the skeletal muscle, 41,42 brain and autonomic nervous system, [43][44][45] or other organs, such as the liver and pancreas. 21,46,47 In addition, because RAS blockade prevents increases in leptin, glucose, and insulin, as well as activation of the intrarenal RAS, these studies do not illustrate which of the defects comes first, metabolic or renal, or which is directly or secondarily prevented by RAS blockade. Other studies presented below shed greater light on this point.…”

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

confidence: 93%

“…We assessed effects of long-term RAS blockade on components of the intrarenal RAS in Wistar rats, a well-characterized model of aging with a life span of Ϸ24 months of age. 20,21,24,25 When treated for 22 months starting at 2 months of age with either losartan or enalapril, these rats have lower SBPs than vehicletreated older control rats. 26 Treated rats also have a higher mitochondrial number, better learning and memory, less cardiac and renal fibrosis, and an extended life span.…”

Section: Differential Regulation Of Circulating and Intrarenal Ras Dumentioning

confidence: 99%

“…The fact that plasma Ang peptides increase dramatically with long-term RAS blockade and urinary levels of the peptides decline renders filtration as the predominant source of urinary peptides unlikely. Although suppression of the intrarenal RAS may be responsible for the renoprotective effects, 21 treated rats had lower pressure and improved overall renal function 28 ; thus, it is not clear to what extent lower pressure contributes to improved renal function and secondarily to lower levels of urinary RAS peptides or vice versa. Because there was no young control group, it is not possible to determine whether lower intrarenal RAS in treated animals reflects the maintenance of normal young urinary peptide levels or lowering of RAS components below levels seen in young adult rats.…”

Section: Differential Regulation Of Circulating and Intrarenal Ras Dumentioning

confidence: 99%

See 2 more Smart Citations

Lewis K. Dahl Memorial Lecture

Diz

2008

Hypertension

View full text Add to dashboard Cite

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...

show abstract

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

confidence: 93%

Section: Differential Regulation Of Circulating and Intrarenal Ras Dumentioning

confidence: 99%

Section: Differential Regulation Of Circulating and Intrarenal Ras Dumentioning

confidence: 99%

See 1 more Smart Citation

Lewis K. Dahl Memorial Lecture

Diz

2008

Hypertension

View full text Add to dashboard Cite

show abstract

“…La suractivation du système rénine-angiotensine-aldostérone (RAAS) serait à l'origine de la formation de glomérulosclérose 3 . Ainsi, des inhibiteurs du récepteur de l'angiotensine Agtr-1a, dont la surexpression des transcrits a été détectée par RTqPCR en cas de glomérulosclérose chez les souris âgées, permettent de diminuer ces lésions en conditions normotensives [7]. Le mécanisme de cette suractivation impliquerait la production, par les cellules épithéliales rénales en sénes-cence, de composés qui activeraient …”

Section: L'éliminationunclassified

L’élimination des cellules sénescentes : vers un avenir meilleur ?

et al. 2016

View full text Add to dashboard Cite

“…As aging progresses the main tubulointerstitial alterations are characterized by tubular atrophy, dilatation of the lumen, thickening of the tubular basement membrane, and flattening of the covering epithelium (7). This is associated with an expansion of interstitial fibrosis and mononuclear infiltration (8). Intrarenal vascular changes also contribute to renal dysfunction which is a key component of advanced age (9).…”

Section: Introductionmentioning

confidence: 99%