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(Hypertension. 1997;29:205.)
© 1997 American Heart Association, Inc.

Arthur C. Corcoran Memorial Lecture

Role of Nitric Oxide in Modulating the Long-term Renal and Hypertensive Actions of Norepinephrine

Joey Granger; Christine Schnackenberg; Jackie Novak; Brett Tucker; Todd Miller; Stephen Morgan; Salah Kassab

From the Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Miss.

Correspondence to Joey P. Granger, PhD, Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 N State St, Jackson, MS 39216-4505. E-mail JPG{at}fiona.umsmed.edu

We have previously reported that nitric oxide (NO) plays an important role in protecting the renal vasculature from acute norepinephrine-induced vasoconstriction. The purpose of this study was to determine the importance of this interaction between NO and norepinephrine in long-term control of renal hemodynamics and arterial pressure. To achieve this goal, we examined the effects of an intrarenal infusion of norepinephrine (NE) (0.1 µg·kg^-1·min^-1) for 7 days in conscious, chronically instrumented control dogs and in dogs pretreated with a synthesis inhibitor, L-NAME (3 µg·kg^-1·min^-1 intrarenally). Both groups of dogs also received captopril (15 µg·kg^-1·min^-1) plus angiotensin II intravenously to clamp the renin-angiotensin system throughout the protocol. In control dogs (n=6), intrarenal infusion of NE decreased renal plasma flow by 9% (134±10 to 122±14 mL/min) and glomerular filtration rate by 16% (49±4 to 41±5 mL/min) while having no effect on mean arterial pressure (100±3 to 98±4 mm Hg). In marked contrast, in dogs pretreated with intrarenal L-NAME (n=9), NE decreased renal plasma flow by 37% (129±8 to 81±16 mL/min) and glomerular filtration rate by 32% (47±3 to 32±5 mL/min) while increasing mean arterial pressure from 104±5 to 113±6 mm Hg. The results of this study demonstrate that NO plays an important role in modulating the long-term actions of NE on renal function and arterial pressure.

Key Words: endothelial factors • kidney • renal hemodynamics • arterial pressure

Abbreviations: GFR = glomerular filtration rate • L-NAME = N-nitro-L-arginine methyl ester • MAP = mean arterial pressure • RPF = renal plasma flow • RVR = renal vascular resistance

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