Renal intramedullary infusion of L-arginine prevents reduction of medullary blood flow and hypertension in Dahl salt-sensitive rats

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.