Published Online
on January 12, 2004

A more recent version of this article appeared on February 1, 2004

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Submitted on June 11, 2003
Revised on July 2, 2003

Dietary NaCl Regulates Renal Aminopeptidase N: Relevance to Hypertension in the Dahl Rat

Mariam Farjah; Theressia L. Washington; Bryan P. Roxas; David L. Geenen; and Robert S. Danziger^*

From the Section of Cardiology (M.F., T.L.W., B.P.R., D.L.G., R.S.D.), Department of Medicine, University of Illinois at Chicago, and West Side Division Veterans Administration (M.F., B.P.R., R.S.D.), Chicago Health Care System, Chicago, Ill.

^* To whom correspondence should be addressed. E-mail: Rdanziger{at}aol.com.

Abstract--Aminopeptidase N (APN) is an abundant metallohydrolase in the brush border of kidney proximal tubule cells that degrades angiotensin III (Ang III) to angiotensin IV (Ang IV) and, along with dipeptidylaminopeptidase, degrades Ang IV. We examined the impact of a high-salt diet on renal APN activity and transcript abundance in the Sprague-Dawley and Dahl salt-sensitive (SS/Jr) rat strains. APN transcript abundance and protein abundance were 2-fold greater (P<0.05; n=6) in the kidneys of Sprague-Dawley and Lewis rats ingesting 8% versus 0.3% salt diets, suggesting that increased aminopeptidase activity may contribute to decreased renal sodium uptake during adaptation to a high-salt diet. In contrast, renal APN transcript abundance and activity were the same in Dahl SS/Jr rats ingesting 8.0% versus 0.3% salt diets. The APN gene was mapped, using a radiation-hybrid panel, to known quantitative loci on chromosome 1 for blood pressure in the Dahl SS/Jr rat. The results suggest that the APN gene is a good candidate for salt-sensitivity in the Dahl SS/Jr rat.

Key words: sodium • kidney • Dahl rat • angiotensin • hypertension

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