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

A role for reduced renal nitric oxide production has been proposed as a mec hanism responsible for hypertension in Dahl "salt-sensitive" rats. The pres ent 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 det ermine if delivery of L- or D-arginine into the renal medulla of Dahl S rat s would change the responses to high salt. Optical fibers were implanted in to the renal cortex and inner medulla for daily recording of cortical and m edullary blood flows using laser-Doppler flowmetry, Indwelling aortic cathe ters 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 b lood flow was unchanged. In Dahl R rats, mean arterial pressure averaged 11 7+/-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 mu g . kg(-1) . min(-1) ) exhibited no changes of mean arterial pressure or regional renal blood fl ow during the 5 days of 4.0% salt intake. Medullary infusion of D-arginine (300 mu g . kg(-1) . min(-1)) did not prevent the development of hypertensi on 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 administr ation of L-arginine can normalize. Furthermore, early reductions of medulla ry blood flow in Dahl S rats with high salt intake probably contribute to t he development of hypertension.