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Departments of 2 Physiology and 1 Internal Medicine, University of Michigan, Ann Arbor, Michigan 48104; and 3 National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892
The present studies were undertaken to determine the effect of dietary salt intake on the renal expression of cyclooxygenase-1 (COX-1) and -2 (COX-2). Protein levels were assessed by Western blotting, and mRNA expression was assessed by reverse transcription-polymerase chain reaction (RT-PCR) on cDNA prepared from kidney regions, dissected nephron segments, and cultured renal cells. Both isoforms were expressed at high levels in inner medulla (IM), with low levels detected in outer medulla and cortex. COX-1 mRNA was present in the glomerulus and all along the collecting duct, whereas COX-2 mRNA was restricted to the macula densa-containing segment (MD), cortical thick ascending limb (CTAL), and, at significantly lower levels, in the inner medullary collecting duct. Both isoforms were highly expressed at high levels in cultured medullary interstitial cells and at lower levels in primary mesangial cells and collecting duct cell lines. Maintaining rats on a low- or high-NaCl diet for 1 wk did not affect expression of COX-1. In IM of rats treated with a high-salt diet, COX-2 mRNA increased 4.5-fold, and protein levels increased 9.5-fold. In contrast, cortical COX-2 mRNA levels decreased 2.9-fold in rats on a high-salt diet and increased 3.3-fold in rats on a low-salt diet. A low-salt diet increased COX-2 mRNA 7.7-fold in MD and 3.3-fold in CTAL. Divergent regulation of COX-2 in cortex and medulla by dietary salt suggests that prostaglandins in different kidney regions serve different functions, with medullary production playing a role in promoting the excretion of salt and water in volume overload, whereas cortical prostaglandins may protect glomerular circulation in volume depletion.
prostaglandin H synthase; inner medulla; renal interstitial cell; macula densa; prostaglandins; sodium chloride
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F. Rodriguez, M. T. Llinas, J. D. Gonzalez, J. Rivera, and F. J. Salazar Renal Changes Induced by a Cyclooxygenase-2 Inhibitor During Normal and Low Sodium Intake Hypertension, August 1, 2000; 36(2): 276 - 281. [Abstract] [Full Text] [PDF]
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H.-F. Cheng, J.-L. Wang, M.-Z. Zhang, James. A. McKanna, and R. C. Harris Nitric oxide regulates renal cortical cyclooxygenase-2 expression Am J Physiol Renal Physiol, July 1, 2000; 279(1): F122 - F129. [Abstract] [Full Text] [PDF]
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U. C. Kopp, M. Z. Cicha, L. A. Smith, J. Z. Haeggstrom, B. Samuelsson, and T. Hokfelt Cyclooxygenase-2 Involved in Stimulation of Renal Mechanosensitive Neurons Hypertension, January 1, 2000; 35(1): 373 - 378. [Abstract] [Full Text] [PDF]
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T. R. Traynor, A. Smart, J. P. Briggs, and J. Schnermann Inhibition of macula densa-stimulated renin secretion by pharmacological blockade of cyclooxygenase-2 Am J Physiol Renal Physiol, November 1, 1999; 277(5): F706 - F710. [Abstract] [Full Text] [PDF]
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T. Yang, J. B. Schnermann, and J. P. Briggs Regulation of cyclooxygenase-2 expression in renal medulla by tonicity in vivo and in vitro Am J Physiol Renal Physiol, July 1, 1999; 277(1): F1 - F9. [Abstract] [Full Text] [PDF]
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T. Yang, D. Sun, Y. G. Huang, A. Smart, J. P. Briggs, and J. B. Schnermann Differential regulation of COX-2 expression in the kidney by lipopolysaccharide: role of CD14 Am J Physiol Renal Physiol, July 1, 1999; 277(1): F10 - F16. [Abstract] [Full Text] [PDF]
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