α2-Adrenergic receptor-mediated increase in NO production buffers renal medullary vasoconstriction

Abstract

The present study was designed to investigate the role of nitric oxide (NO) in modulating the adrenergic vasoconstrictor response of the renal medullary circulation. In anesthetized rats, intravenous infusion of norepinephrine (NE) at a subpressor dose of 0.1 μg · kg−1 · min−1 did not alter renal cortical (CBF) and medullary (MBF) blood flows measured by laser-Doppler flowmetry nor medullary tissue Po 2(Pm o 2) as measured by a polarographic microelectrode. In the presence of the NO synthase inhibitor nitro-l-arginine methyl ester (l-NAME) in the renal medulla, intravenous infusion of NE significantly reduced MBF by 30% and Pm o 2 by 37%. With the use of an in vivo microdialysis-oxyhemoglobin NO-trapping technique, we found that intravenous infusion of NE increased interstitial NO concentrations by 43% in the renal medulla. NE-stimulated elevations of tissue NO were completely blocked either by renal medullary interstitial infusion ofl-NAME or the α2-antagonist rauwolscine (30 μg · kg−1 · min−1). Concurrently, intavenous infusion of NE resulted in a significant reduction of MBF in the presence of rauwolscine. The α1-antagonist prazosin (10 μg · kg−1 · min−1 renal medullary interstitial infusion) did not reduce the NE-induced increase in NO production, and NE increased MBF in the presence of prazosin. Microdissection and RT-PCR analyses demonstrated that the vasa recta expressed the mRNA of α2B-adrenergic receptors and that medullary thick ascending limb and collecting duct expressed the mRNA of both α2A- and α2B-adrenergic receptors. These subtypes of α2-adrenergic receptors may mediate NE-induced NO production in the renal medulla. We conclude that the increase in medullary NO production associated with the activation of α2-adrenergic receptors counteracts the vasoconstrictor effects of NE in the renal medulla and may play an important role in maintaining a constancy of MBF and medullary oxygenation.