Role of renal cortical cyclooxygenase-2 expression in hyperfiltration in rats with high-protein intake.
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.
Yao
Bing
B
Division of Nephrology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2372, USA.
Xu
Jie
J
Qi
Zhonghua
Z
Harris
Raymond C
RC
Zhang
Ming-Zhi
MZ
D000818:Animals; D051546:Cyclooxygenase 2 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D004044:Dietary Proteins / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D005919:Glomerular Filtration Rate / Q000187:drug effects* / Q000502:physiology*; D007672:Kidney Cortex / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D008297:Male; D052248:Nitric Oxide Synthase Type I / Q000032:analysis / Q000235:genetics / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000032:analysis / Q000235:genetics / Q000502:physiology; D012965:Sodium Chloride / Q000378:metabolism
D004044:Dietary Proteins; D012965:Sodium Chloride; D052248:Nitric Oxide Synthase Type I; D051546:Cyclooxygenase 2; D012083:Renin