NEURAL NITRIC-OXIDE SYNTHASE IN THE RENAL MEDULLA AND BLOOD-PRESSURE REGULATION

We studied the effect of selective inhibition of the neural isoform of nitric oxide synthase in the rat renal medulla in conscious Sprague-D awley rats. Continuous renal medullary interstitial infusion of an ant isense oligonucleotide complementary to the initiation region of the m RNA for neural nitric oxide synthase increased blood pressure 14 +/- 1 mm Hg in rats maintained on a high sodium intake. Medullary interstit ial infusion of saline vehicle or a scrambled oligonucleotide probe fa iled to alter blood pressure in separate groups of high salt control r ats. Renal medullary interstitial infusion of the antisense oligonucle otide significantly decreased the level of neural nitric oxide synthas e in the renal medulla by 53 +/- 8% and decreased total renal medullar y nitric oxide synthase activity by 28 +/- 8%. No alterations were det ected in the levels of inducible nitric oxide synthase or beta-actin i n the antisense oligonucleotide-infused rats. To confirm the antisense oligonucleotide data, we administered a mechanistically different inh ibitor of neural nitric oxide synthase, 7-nitroindazole, to an additio nal group of rats maintained on a high salt diet. Direct renal medulla ry interstitial infusion of this selective enzyme inhibitor significan tly increased mean arterial pressure (15 +/- 6 mm Hg) and decreased to tal renal medullary nitric oxide synthase activity by 37 +/- 12% in ra ts on a high sodium diet. The present experiments demonstrate a role f or the neural isoform of nitric oxide synthase in the long-term contro l of blood pressure in the presence of a high salt diet.