alpha(2)-Adrenergic receptor-mediated increase in NO production buffers renal medullary vasoconstriction

The present study was designed to investigate the role of nitric oxide (NO) in modulating the adrenergic vasoconstrictor response of the renal medulla ry circulation. In anesthetized rats, intravenous infusion of norepinephrin e (NE) at a subpressor dose of 0.1 mu g . kg(-1) . min(-1) did not alter re nal cortical (CBF) and medullary (MBF) blood flows measured by laser-Dopple r flowmetry nor medullary tissue PO2 (PmO2) as measured by a polarographic microelectrode. In the presence of the NO synthase inhibitor nitro-L-argini ne methyl ester (L-NAME) in the renal medulla, intravenous infusion of NE s ignificantly reduced MBF by 30% and PmO2 by 37%. With the use of an in vivo microdialysis-oxyhemoglobin NO-trapping technique, we found that intraveno us infusion of NE increased interstitial NO concentrations by 43% in the re nal medulla. NE-stimulated elevations of tissue NO were completely blocked either by renal medullary interstitial infusion of L-NAME or the alpha(2)-a ntagonist rauwolscine (30 mu g . kg(-1) . min(-1)). Concurrently, intraveno us infusion of NE resulted in a significant reduction of MBF in the presenc e of rauwolscine. The alpha(1)-antagonist prazosin (10 mu g . kg(-1) . min( -1) renal medullary interstitial infusion) did not reduce the NE-induced in crease in NO production, and NE increased MBF in the presence of prazosin. Microdissection and RT-PCR analyses demonstrated that the vasa recta expres sed the mRNA of alpha(2B)-adrenergic receptors and that medullary thick asc ending limb and collecting duct expressed the mRNA of both alpha(2A)- and a lpha(2B)-adrenergic receptors. These subtypes of alpha(2)-adrenergic recept ors may mediate NE-induced NO production in the renal medulla. We conclude that the increase in medullary NO production associated with the activation of alpha(2)-adrenergic receptors counteracts the vasoconstrictor effects o f NE in the renal medulla and may play an important role in maintaining a c onstancy of MBF and medullary oxygenation.