Renal effects of prolonged high protein intake and COX2 inhibition on hypertensive rats with altered renal development

Cyclooxygenase 2 (COX2) is involved in regulating renal hemodynamics after renal ablation. It is also known that high protein intake (HPI) leads to a deterioration of renal function when there is preexisting renal disease and that there are important gender differences in the regulation of renal function. This study tested the hypothesis that the role of COX2 in regulating renal function and the renal hemodynamic effects elicited by HPI are enhanced when nephrogenesis is altered during renal development. It was also expected that the role of COX2 and the effects elicited by HPI are age and sex dependent. Newborn Sprague-Dawley rats were treated with an AT1 ANG II receptor antagonist during the nephrogenic period (ARAnp). Experiments were performed at 3–4 and 10–11 mo of age. Arterial pressure was elevated ( P < 0.05) at both ages and in both sexes of ARAnp-treated rats. Renal COX2 expression was only elevated ( P < 0.05) at 10–11 mo of age in both sexes of ARAnp-treated rats. COX2 inhibition induced greater renal vasoconstriction in male and female hypertensive than in normotensive rats at both ages. HPI did not induce glomerular filtration rate (GFR) in the youngest hypertensive rats and in the oldest female hypertensive rats. However, the GFR decreased during HPI (0.63 ± 0.07 to 0.19 ± 0.05 ml/min) in the oldest male hypertensive rats. The HPI-induced increment in proteinuria was greater ( P < 0.05) in male (99 ± 22 mg/day) than in female (30 ± 8 mg/day) hypertensive rats. These results show that COX2 plays an important role in the regulation of renal function when renal development is altered and that prolonged HPI can lead to a renal insufficiency in males but not in females with reduced nephron endowment.

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High Protein Intake Associates with Cardiovascular Events but not with Loss of Renal Function

Journal of the American Society of Nephrology ◽

10.1681/asn.2008060649 ◽

2009 ◽

Vol 20 (8) ◽

pp. 1797-1804 ◽

Cited By ~ 54

Author(s):

Nynke Halbesma ◽

Stephan J.L. Bakker ◽

Desiree F. Jansen ◽

Ronald P. Stolk ◽

Dick De Zeeuw ◽

...

Keyword(s):

Renal Function ◽

Protein Intake ◽

Cardiovascular Events ◽

High Protein ◽

High Protein Intake

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Role of renal cortical cyclooxygenase-2 expression in hyperfiltration in rats with high-protein intake

AJP Renal Physiology ◽

10.1152/ajprenal.00500.2005 ◽

2006 ◽

Vol 291 (2) ◽

pp. F368-F374 ◽

Cited By ~ 27

Author(s):

Bing Yao ◽

Jie Xu ◽

Zhonghua Qi ◽

Raymond C. Harris ◽

Ming-Zhi Zhang

Keyword(s):

Protein Intake ◽

Cyclooxygenase 2 ◽

High Protein ◽

Kidney Cortex ◽

High Protein Intake ◽

Protein Loading ◽

Renal Ablation ◽

Cox 2 ◽

Arteriolar Tone ◽

Oxide Synthase

Renal cortical cyclooxygenase-2 (COX-2) is restricted to the macula densa and adjacent cortical thick ascending limbs (MD/cTALH). Renal cortical COX-2 increases in response to diabetes and renal ablation, both of which are characterized by hyperfiltration and reduced NaCl delivery to the MD due to increased proximal NaCl reabsorption. High-protein intake also induces hyperfiltration and decreases NaCl delivery to the MD due to increased NaCl reabsorption proximally. We investigated whether high protein induces cortical COX-2 and whether cortical COX-2 contributes to high protein-induced hyperfiltration and increased intrarenal renin biosynthesis. Cortical COX-2 increased after protein loading but decreased after protein restriction. COX-2 inhibition attenuated high protein-induced hyperfiltration but had no effect on high protein-induced intrarenal renin elevation. Therefore, induction of cortical COX-2 contributed to high protein-induced hyperfiltration but not intrarenal renin elevation. In the kidney cortex, neuronal nitric oxide synthase (nNOS) is also localized to the MD, and interactions between intrarenal nNOS and COX-2 systems have been proposed. Cortical COX-2 elevation seen in salt restriction was blocked by nNOS inhibiton. Cortical nNOS expression also increased after protein loading, and inhibition of nNOS activity completely reversed high protein-induced cortical COX-2 elevation and hyperfiltration. These results indicate that NO is a mediator of high protein-induced cortical COX-2 elevation and suggest that both intrarenal nNOS and COX-2 systems appear to regulate afferent arteriolar tone and subsequent hyperfiltration seen in high-protein intake.

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Do Regular High Protein Diets Have Potential Health Risks on Kidney Function in Athletes?

International Journal of Sport Nutrition and Exercise Metabolism ◽

10.1123/ijsnem.10.1.28 ◽

2000 ◽

Vol 10 (1) ◽

pp. 28-38 ◽

Cited By ~ 46

Author(s):

Jacques R. Poortmans ◽

Olivier Dellalieux

Keyword(s):

Renal Function ◽

Kidney Function ◽

Protein Intake ◽

Excretion Rate ◽

Albumin Excretion Rate ◽

High Protein ◽

Calcium Excretion ◽

Potential Health ◽

High Protein Intake ◽

Amino Acid Intake

Excess protein and amino acid intake have been recognized as hazardous potential implications for kidney function, leading to progressive impairment of this organ. It has been suggested in the literature, without clear evidence, that high protein intake by athletes has no harmful consequences on renal function. This study investigated body-builders (BB) and other well-trained athletes (OA) with high and medium protein intake, respectively, in order to shed light on this issue. The athletes underwent a 7-day nutrition record analysis as well as blood sample and urine collection to determine the potential renal consequences of a high protein intake. The data revealed that despite higher plasma concentration of uric acid and calcium. Group BB had renal clearances of creatinine, urea, and albumin that were within the normal range. The nitrogen balance for both groups became positive when daily protein intake exceeded 1.26 g · kg−1 but there were no correlations between protein intake and creatinine clearance, albumin excretion rate, and calcium excretion rate. To conclude, it appears that protein intake under 2.8 g·kg−1 does not impair renal function in well-trained athletes as indicated by the measures of renal function used in this study.

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