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(Hypertension. 2002;39:287.)
© 2002 American Heart Association, Inc.

Scientific Contributions

Cationic Amino Acid Transport in the Renal Medulla and Blood Pressure Regulation

Masao Kakoki; Weili Wang; David L. Mattson

From the Department of Physiology, Medical College of Wisconsin, Milwaukee.

Correspondence to David L. Mattson, Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226. E-mail dmattson{at}mcw.edu

Previous studies have indicated that NO synthesis in isolated inner medullary collecting duct cells is reduced by cationic amino acids that compete with L-arginine for cellular uptake. In the present study, we investigated the effects of chronic renal medullary infusion of cationic amino acids on renal NO concentration and mean arterial pressure (MAP) in Sprague-Dawley rats. Renal medullary infusion of L-ornithine (50 µg/kg per min) or L-lysine (50 µg/kg per min) markedly decreased NO in the medulla (vehicle, 124±11 nmol/L; L-ornithine, 45±4 nmol/L; L-lysine, 42±6 nmol/L) and increased MAP (vehicle, 111±7 mm Hg; L-ornithine, 143±6 mm Hg; L-lysine, 148±3 mm Hg) after 5 days of infusion. In contrast, intravenous infusion of the same dose of L-ornithine or L-lysine for 5 days increased plasma concentration to levels similar to those observed with intramedullary infusion but did not change NO in the medulla or alter MAP. Furthermore, the NO-suppressing and hypertensive effects of medullary interstitial infusion of L-ornithine (50 µg/kg per min) were attenuated by simultaneous infusion of L-arginine (500 µg/kg per min; NO, 97±10 nmol/L; MAP, 124±3 mm Hg). A 5-day infusion of an antisense oligonucleotide against CAT-1 (18-mer, 8.3 nmol/h) significantly decreased CAT-1 protein in the medulla, decreased NO in the medulla (scrambled oligo, 124±10 nmol/L; antisense oligo, 67±11 nmol/L), and increased MAP (scrambled oligo, 113±2 mm Hg; antisense oligo, 130±2 mm Hg). These results suggest that uptake of L-arginine by cationic amino acid transport systems in the renal medulla plays an important role in the regulation of medullary NO and MAP in rats.

Key Words: arterial pressure • amino acid • kidney • nitric oxide • renal blood flow

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