Renal programming: cause for concern?

Kett, Michelle M; Denton, Kate M.

doi:10.1152/ajpregu.00791.2010

Cited by 120 publications

(156 citation statements)

References 158 publications

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“…While not impacting baseline arterial pressure, recent studies have suggested that a low nephron number does increase the risk of developing hypertension in animals exposed to secondary adverse stimuli such as a highsalt diet (12). We hypothesized that if a low nephron endowment is associated with an increased risk for hypertension and its associated pathologies, then a high nephron endowment may act in an opposing, protective, manner.…”

Section: Discussionmentioning

confidence: 94%

“…Yet the number of nephrons in human kidneys has been found to be highly variable, with a 13-fold range recently reported (10). A low nephron endowment has long been identified as a risk factor for the development of hypertension and chronic kidney disease (12,18,27), particularly in the presence of secondary insults, such as a high-salt diet (6,17,22). However, the converse hypothesis, that a high nephron number decreases the risk of hypertension and renal disease, has not been explored experimentally, despite the findings of a recent human autopsy study in which probability of presenting with hypertension was decreased in Caucasian Americans with a nephron endowment Ͼ876,300 compared with subjects with a lower nephron endowment (21).…”

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confidence: 99%

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High nephron endowment protects against salt-induced hypertension

Walker

Cai

Caruana

et al. 2012

American Journal of Physiology-Renal Physiology

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Walker KA, Cai X, Caruana G, Thomas MC, Bertram JF, Kett MM. High nephron endowment protects against salt-induced hypertension. Am J Physiol Renal Physiol 303: F253-F258, 2012. First published May 9, 2012 doi:10.1152/ajprenal.00028.2012.-While low nephron number is associated with increased risk of developing cardiovascular and renal disease, the functional consequences of a high nephron number are unknown. We tested the hypothesis that a high nephron number provides protection against hypertensive and renal insults. Mean arterial pressure (MAP) and renal function were characterized in male wild-type (WT) and transforming growth factor-␤2 heterozygous (Tgfb2 ϩ/Ϫ ) mice under basal conditions and following a chronic high-salt diet. Kidneys were collected for unbiased stereological analysis. Baseline MAP and renal function were indistinguishable between genotypes. The chronic high-salt diet (5% NaCl for 4 wk followed by 8% NaCl for 4 wk) led to similar step-wise increases in urine volume, Na ϩ excretion, and albuminuria in the genotypes. The 5% NaCl diet induced modest and similar increases in MAP (3.5 Ϯ 1.6 and 3.4 Ϯ 0.8 mmHg in WT and Tgfb2 ϩ/Ϫ , respectively). After the step up to the 8% NaCl diet, MAP increased further in WT (ϩ15.9 Ϯ 5.1 mmHg), but not Tgfb2 ϩ/Ϫ (Ϫ0.1 Ϯ 1.0 mmHg), mice. Nephron number was 30% greater in Tgfb2 ϩ/Ϫ than WT mice and was not affected by the chronic high-salt diet. Mean glomerular volume was lower in Tgfb2 ϩ/Ϫ than WT mice, and the chronic high-salt diet induced significant glomerular hypertrophy. In a separate cohort of mice, an acute, 7-day, 8% NaCl diet induced similar rises in MAP in the genotypes. This is the first study to examine the physiological characteristics of a model of high nephron number, and the findings are consistent with this phenotype providing protection against chronic, but not acute, hypertensive insults. renal stereology; renal function; mean arterial pressure

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Section: Discussionmentioning

confidence: 94%

mentioning

confidence: 99%

High nephron endowment protects against salt-induced hypertension

Walker

Cai

Caruana

et al. 2012

American Journal of Physiology-Renal Physiology

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“…11,12 Moreover, the trajectory of the relationship between age and arterial pressure is influenced by birth weight and growth in childhood. 13 Indeed, in a recent large-cohort study, linear growth velocity (height) between 8 and 13 years in boys was shown to be positively associated with adult arterial pressure.…”

Section: Sex-related Differences In the Trajectory Of Arterial Pressumentioning

confidence: 99%

“…18 Animal studies have recapitulated these findings and allowed exploration of the underlying mechanisms, which are sexually dimorphic. 12,19 Testosterone has been clearly demonstrated to contribute to the programming of adult hypertension in growth-restricted male rat offspring. 20 Recently, this same group has defined a role for increased oxidative stress in determining kidney function and arterial pressure in growth-restricted male offspring, an effect that was reversed by antioxidant therapy.…”

Section: Sex-related Differences In the Trajectory Of Arterial Pressumentioning

confidence: 99%

Sex-Related Differences in Hypertension

2013

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M uch of what we understand about the regulation of arterial pressure and extracellular fluid volume has been derived from studies in men. Although the responses that can be mounted against major physiological challenges to extracellular fluid volume (hemorrhage/dehydration) are essentially similar in men and women, there are marked sex-related differences in the regulation of renal and cardiovascular physiology. These possibly underpin the greater risk of renal and cardiovascular disease (CVD) in men and, conversely, confer the relative protection from these conditions in women, at least until menopause. In recent years, advances have been made in understanding the mechanistic bases for sex-related differences in CVD and these have been reviewed in detail.1-3 Therefore, the purpose of this report is to provide an update of findings in the past few years. Sex-Specific Risk Factors and Clinical OutcomesIncreasingly, studies are incorporating sex as a factor into their analyses.Although not all studies demonstrate a sex-specific interaction, 4-7 many do, exemplifying the mantra, seek and ye shall find; this appears to be particularly true for sex-related differences in CVD. In recent years, evidence that women have smaller and stiffer hearts because of a greater collagen content has received a good deal of attention for the reason that it may explain some of the puzzling differences in clinical signs of CVD between men and women. Puntmann et al 8 examined aortic stiffness by pulse wave velocity and ventricular deformation indices using MRI both at rest and during dobutamine challenge in elderly men and women. At rest, women had greater aortic stiffness and ventricular deformation than men. Moreover, sex-related differences were observed during stress because men had increased longitudinal and circumferential ventricular deformation during dobutamine challenge, whereas women only had an increase in circumferential deformation. 8 These data suggest that differential loading of the aortic reservoir in men occurs because of increases in longitudinal and circumferential ventricular contraction, an effect independent of aortic stiffness. However, dynamic challenge with dobutamine induced only a limited response in women, because although men could improve longitudinal ventricular contraction, women could not. Russo et al 9 reported similar findings of increased arterial stiffness and wave reflection in women compared with those in men. In addition, an inverse relationship between arterial stiffness and left ventricular diastolic function was identified in both sexes. Therefore, higher arterial stiffness may contribute to the greater risk of developing heart failure in the presence of a normal ejection fraction in women. In both men and women, there is a linear increase in arterial stiffness with aging. Although women have increased arterial stiffness, this may be somewhat tempered by female sex steroids during the reproductive years. Following menopause, there is a profound acceleration in arterial stiffening, probably ...

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“…Broadly, these studies showed that cardiovascular, renal, and metabolic disorders could all be programmed by undernutrition. 8 Although these malnutrition models still have significance in today's society, the high rates of obesity in the Western world, and urbanized regions of the developing world, have led to a shift in the field of programming from one of maternal undernutrition to one of maternal overnutrition. As the prevalence of maternal obesity rises, so too has the number of children at risk of fetal programming.…”

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confidence: 99%