Changes in renal hemodynamics and structure in the aging kidney; sexual dimorphism and the nitric oxide system

Baylis, Chris

doi:10.1016/j.exger.2005.01.008

Cited by 78 publications

(60 citation statements)

References 53 publications

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“…Although clearly speculative, the greater glomeruli number by body weight in control females may partly explain why kidney function is more preserved in females than in males during aging. 22 The higher degree of glomerulosclerosis found in our treated males as compared with females may be explained by the fact that SNGFR needs to increase more in males than in females trying to maintain GFR. The increment in SNGFR when nephron number decreases may be secondary to an elevation in glomerular capillary pressure.…”

Section: Discussionmentioning

confidence: 88%

“…The greater glomerulosclerosis in males may also be attributed to the effects of androgens and to the absence of estrogens. 22,23 Tubulointerstitial damage found in the ARA-treated rats was expected, because it is well established that blockade of RAS during nephrogenesis results in tubular dilatation, chronic interstitial inflammation, and fibrosis in the adulthood 9 and that tubular dilatation is an early event followed by a secondary inflammatory response. 24 It is clear that tubulointerstitial injury in the renal cortex and renal medulla was also greater in males than in females, with a similar decrease in nephron number.…”

Section: Discussionmentioning

confidence: 99%

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Sex Differences in the Renal Changes Elicited by Angiotensin II Blockade During the Nephrogenic Period

et al. 2007

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Abstract-The renin-angiotensin system plays an important role in renal development. However, it is unknown whether reduction in angiotensin II effects during the nephrogenic period leads to different renal alterations in males and females during the adult age. The aim of this study was to evaluate whether the role of angiotensin II on renal development is sex dependent and whether there are sex differences in blood pressure, renal hemodynamics, and severity of renal damage during adult life when nephrogenesis is altered by blocking angiotensin II effects. Newborn Sprague-Dawley rats were treated with an angiotensin II type 1 receptor antagonist (L-158.809; 7 mg/kg per day) during the first 2 weeks of life. At 3 months of age, changes in blood pressure, albuminuria, and renal hemodynamics were assessed, and stereological and histopathologic studies were performed. Blood pressure increased (127Ϯ0.5 versus 115Ϯ0.7 mm Hg in control rats; PϽ0.05) and nephron number decreased (37%; PϽ0.05) similarly in treated males and females. However, only males had an elevation in albuminuria (5.92Ϯ1.65 versus 0.33Ϯ0.09 mg per day in control rats; PϽ0.05), a fall in glomerular filtration rate (12.6%; PϽ0.05), and a significant decrease in papillary volume (42%; PϽ0.05). Mean glomerular volume, glomerulosclerosis, arteriolar hypertrophy, and tubulointerstitial damage in cortex and medulla were also higher (PϽ0.05) in angiotensin II type 1 receptor antagonist-treated males than in treated females. The results of this study suggest that females seem to be more protected than males to the renal consequences of reducing angiotensin II effects during renal development.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Sex Differences in the Renal Changes Elicited by Angiotensin II Blockade During the Nephrogenic Period

et al. 2007

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“…[23][24][25] In support of these possibilities, it has been shown that the sexual differences in renal damage may be explained by an decline in NO in aged male but not in aged female rats, 24 by the damaging influence of androgens in males, and/or the protective effects of estrogens. [23][24][25] The hypothesis that angiotensin II may be involved in the observed renal damage during aging is based on studies demonstrating the following: (1) the renin-angiotensin activity is enhanced in several experimental models with a reduced nephron endowment 15,26 ; (2) angiotensin II is a potent growth factor 27 ; and (3) angiotensin II effects are enhanced in the presence of androgens but reduced when estrogens are elevated. 24 In summary, the current study emphasizes the importance of COX2-derived metabolites in the regulation of nephrogenesis.…”

Section: Discussionmentioning

confidence: 94%

“…[23][24][25] The hypothesis that angiotensin II may be involved in the observed renal damage during aging is based on studies demonstrating the following: (1) the renin-angiotensin activity is enhanced in several experimental models with a reduced nephron endowment 15,26 ; (2) angiotensin II is a potent growth factor 27 ; and (3) angiotensin II effects are enhanced in the presence of androgens but reduced when estrogens are elevated. 24 In summary, the current study emphasizes the importance of COX2-derived metabolites in the regulation of nephrogenesis. We have reported new evidence showing that a slight impairment of renal development may lead to a significant increment in arterial pressure and to a sex-dependent accelerated deterioration of the renal structure and renal function.…”

Section: Discussionmentioning

confidence: 99%

Hypertension and Sex Differences in the Age-Related Renal Changes When Cyclooxygenase-2 Activity Is Reduced During Nephrogenesis

et al. 2009

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Abstract-Several studies have proposed that cyclooxygenase-2 (COX2) is involved in the regulation of nephrogenesis and that an impaired nephrogenesis may induce the development of hypertension. This study was designed to test the hypothesis that the decrease of COX2 activity leads to a reduction in nephron number, an increase in arterial pressure, and age-dependent renal alterations that are greater in male than in female rats. Arterial pressure was measured from the first to the 16th month of life in rats treated with vehicle or a COX2 inhibitor during the nephrogenic period. Stereological and histological evaluations and renal function studies were performed at different ages. Arterial pressure increased (14%; PϽ0.05) and nephron number decreased (17%; PϽ0.05) to similar levels in male and female COX2-treated rats. However, glomerular filtration rate (31%) and renal plasma flow (25%) decreased (PϽ0.05) in male but not in female COX2-treated rats. A greater (PϽ0.05) age-dependent elevation in glomerular hypertrophy was also found in male COX2-treated rats compared with their female littermates. Glomerulosclerosis and tubulointerstitial damage in renal cortex and medulla were also significantly enhanced in male but not in female aged COX2-treated rats.Our results demonstrate that the decrease in COX2 activity during renal development leads to a reduction in nephron number and to an elevation in arterial pressure that are similar in males and females. However, the consequent age-dependent deterioration of the renal structure and renal function is only significantly enhanced in male rats. Key Words: fetal programming Ⅲ glomerulosclerosis Ⅲ renal fibrosis Ⅲ aging Ⅲ proteinuria Ⅲ cyclooxygenases Ⅲ prostaglandins T he importance of cyclooxygenase-2 (COX2)-derived metabolites in the regulation of renal morphogenesis is supported by studies showing that the use of nonsteroidal anti-inflammatory drugs as tocolytics is related to renal abnormalities and renal failure in the neonate 1 and that COX2-deficient mice show a thin nephrogenic cortex and immature glomeruli and tubuli. 2-4 These effects have also been found after the administration of a COX2-specific inhibitor during the nephrogenic period in mice. 5 Furthermore, it is well known that COX2 appears in the developing rodent metanephros starting at embryonic day 16, and it is upregulated in the kidney during the first 2 weeks of life. 6,7 The link among a suboptimal nephron endowment, hypertension, and an age-dependent development of renal damage has been shown in many studies, 8 -11 but nowadays it is unknown whether the reduction in COX2 activity during the nephrogenic period leads to a lower nephron number, hypertension, and a progressive deterioration of the renal structure and function.The objective of this study was to evaluate the effects of COX2 inhibition during the nephrogenic period (COX2 Inh np ) on nephron number and on the age-dependent changes in arterial pressure, renal structure, and renal function. Because recent works of our group have reported s...

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“…In the aged kidney progressive glomerulosclerosis, reduced glomerular filtration rate, and vascular hyalinization all occur concomitantly with the loss of functioning nephrons (18), so that elderly kidneys are more susceptible to failure when other insults are superimposed.…”

Section: Discussionmentioning

confidence: 99%

Supplementation with Essential Amino Acids in Middle Age Maintains the Health of Rat Kidney

Corsetti

Stacchiotti

D’Antona

et al. 2010

Int J Immunopathol Pharmacol

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Chronic kidney diseases are a social and economic problem, and diet has long been recognized as a fundamental modulator of kidney health in human and experimental models. Age-dependent alterations in mitochondrial function playa crucial role in the development of diseases of aging, and mitochondrial disorders have been observed in experimental models of kidney failure. Recently, the beneficial dietary effect of a specific mixture of essential amino acids (EAA) has been studied in elderly subjects, but no data were collected from the kidney. The aim of this study was to assess whether daily supplementation of the diet with EAA at the beginning of senescence could preserve renal health. We used middle-aged (I8-month-old) male Wistar rats fed a standard diet and water ad libitum (M-aged group) or a diet with added EAA (1.5 g/kg per day) dissolved in drinking water for 3 months (M-aged+EAA group). Young (2-month-old) rats fed a standard diet for 3 months were used as controls. Mitochondrial morphology and markers for collagen, cyt-c-oxidase, HSP60, GRP75, eNOS, iNOS, Bax, Bel2 and VEGF were analyzed in glomeruli and tubules. EAA supplementation limited fibrosis and increased the capillary tuft area in the glomeruli of M-aged rats. VEGF and eNOS were enhanced in glomeruli and the peritubular space with the EAA-supplemented diet. Mitochondrial cyt-c oxidase, Bel2, and chaperones increased in the distal tubules of the EAA group to levels similar to those observed in the young group. Mitochondrial area and density after EAA intake did not differ from young groups. The results suggest that prolonged EAA intake could represent a strategy for maintaining the healthy status of the kidney in M-aged animals.Chronic kidney diseases (CKD) and their progression to end-stage renal disease (ESRD) are considerable social and economic problems in all industrialized countries. Each year in Italy, more than 18,000 patients are diagnosed as having CKD (1). The incidence of CKD is strictly linked to age: in patients over 75 years it was almost 7 times that in patients aged 20-39 years and more the twice that in patients aged 40-59 years (2). Therefore, interventions that may prevent the development of CKD in middle age are very important for public health.Reactive oxygen species (ROS) and nitrogen species are responsible for human aging

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Changes in renal hemodynamics and structure in the aging kidney; sexual dimorphism and the nitric oxide system

Cited by 78 publications

References 53 publications

Sex Differences in the Renal Changes Elicited by Angiotensin II Blockade During the Nephrogenic Period

Sex Differences in the Renal Changes Elicited by Angiotensin II Blockade During the Nephrogenic Period

Hypertension and Sex Differences in the Age-Related Renal Changes When Cyclooxygenase-2 Activity Is Reduced During Nephrogenesis

Supplementation with Essential Amino Acids in Middle Age Maintains the Health of Rat Kidney

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