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(Hypertension. 2000;35:418.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Increase in Renal Medullary Nitric Oxide Synthase Activity Protects From Norepinephrine-Induced Hypertension

Mátyás Szentiványi, Jr; Ai-Ping Zou; Celso Y. Maeda; David L. Mattson; Allen W. Cowley, Jr

From the Clinical Research Department, 2nd Institute of Physiology, Semmelweis University of Medicine (M.S.), Budapest, Hungary; the Department of Physiology, Medical College of Wisconsin (A.-P.Z., D.L.M., A.W.C.), Milwaukee; and the Laboratoria de Cardiovascular, Department de Fisiologia, ICBS, UFRGS (C.Y.M.), Brazil.

Correspondence to Allen W. Cowley, Jr, PhD, Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Rd, POB 26509, Milwaukee, WI 53226-0509. E-mail cowley{at}mcw.edu

Abstract—Studies were performed in conscious Sprague-Dawley rats to determine the role of the ₂-adrenergic receptor–mediated increase in the renal medullary nitric oxide synthase (NOS) activity as a counterregulatory mechanism of blood pressure control in response to increased renal adrenergic stimulation. A subpressor dose of norepinephrine (NE, 8 µg · kg^-1 · h^-1) was infused intravenously, and NOS activity was determined with arginine-citrulline conversion by high-performance liquid chromatography in renal cortical and outer and inner medullary tissues. It was found that after 7 days of intravenous NE infusion, NOS activity was significantly higher in both the outer and inner medullary tissues (158±45 versus 30±24 pmol · mg^-1 · h^-1 [outer medulla] and 5.1±0.7 versus 2.0±0.5 nmol · mg^-1 · h^-1 [inner medulla] for NE-treated versus control rats, respectively). To determine whether the increase of NOS activity was mediated through renal medullary ₂-receptors, the receptor antagonist rauwolscine (RAU, 1 µg · kg^-1 · min^-1) was infused via an implanted renal medullary interstitial catheter, and the consequences of intravenous NE administration were evaluated. NOS activity was significantly lower in the RAU-infused animals and did not increase with infusion of NE. To determine the systemic effects of the renal medullary ₂-receptors, studies were performed to determine the consequences of chronic intravenous infusion of subpressor amounts of NE in the presence and absence of renal medullary ₂-receptor inhibition. Under conditions in which RAU was continuously infused into the renal medulla, the same subpressor dose of NE caused sustained and reversible hypertension (mean arterial pressure increased from 120±3 to 131±3 mm Hg). Chronic blunting of the renal medullary NOS activity with N^G-nitro-L-arginine methyl ester (75 µg · kg^-1 · h^-1) also enabled NE to produce a significant rise in mean arterial pressure (from 117±2 to 134±4 mm Hg). We conclude that the hypertensive effects of moderate elevations of renal adrenergic activity were chronically buffered by the ₂-receptor–mediated increase in NOS activity within the renal medulla.

Key Words: norepinephrine • receptors, adrenergic, alpha • rauwolscine • nitric oxide synthase • rats

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