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(Hypertension. 1999;33:446-450.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Renal Intramedullary Infusion of L-Arginine Prevents Reduction of Medullary Blood Flow and Hypertension in Dahl Salt-Sensitive Rats

Noriyuki Miyata; Allen W. Cowley, Jr

From Taisho Pharmaceutical (N.M.), Tokyo, Japan; and the Department of Physiology (A.W.C.), Medical College of Wisconsin, Milwaukee.

Correspondence to Allen W. Cowley, Jr, PhD, Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226. E-mail cowley{at}mcw.edu

Abstract—A role for reduced renal nitric oxide production has been proposed as a mechanism responsible for hypertension in Dahl "salt-sensitive" rats. The present study had 2 goals: first, to determine the relationship between changes in mean arterial pressure and renal cortical and medullary blood flows in unanesthetized Dahl/Rapp salt-sensitive (S) and Dahl/Rapp salt-resistant (R) rats as daily salt intake was increased from 0.4% to 4.0%; second, to determine if delivery of L- or D-arginine into the renal medulla of Dahl S rats would change the responses to high salt. Optical fibers were implanted into the renal cortex and inner medulla for daily recording of cortical and medullary blood flows using laser-Doppler flowmetry. Indwelling aortic catheters were used to record arterial pressure. Increasing salt intake to 4.0% in Dahl S rats increased mean arterial pressure from 128±2.0 to 155±5.0 mm Hg by day 5 of high salt diet; medullary blood flow was reduced 13% by day 2, 24% by day 3 (P<0.05), and 31% by day 5 (P<0.05), whereas cortical blood flow was unchanged. In Dahl R rats, mean arterial pressure averaged 117±5 mm Hg during the 0.4% salt control period and remained unchanged (as did cortical and medullary blood flows) during 5 days of 4.0% salt intake. Dahl S rats that received medullary L-arginine (300 µg · kg^–1 · min^–1) exhibited no changes of mean arterial pressure or regional renal blood flow during the 5 days of 4.0% salt intake. Medullary infusion of D-arginine (300 µg · kg^–1 · min^–1) did not prevent the development of hypertension in Dahl S rats that received 4.0% salt. The results are consistent with the view that Dahl S rats have a reduced capacity to generate nitric oxide within the renal medulla under conditions of high salt, which the administration of L-arginine can normalize. Furthermore, early reductions of medullary blood flow in Dahl S rats with high salt intake probably contribute to the development of hypertension.

Key Words: arginine • blood flow • kidney • nitric oxide • hypertension, renal • rats, Dahl

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