ROLE OF NITRIC-OXIDE IN MODULATING THE LONG-TERM RENAL AND HYPERTENSIVE ACTIONS OF NOREPINEPHRINE

We have previously reported that nitric oxide (NO) plays an important role in protecting the renal vasculature from acute norepinephrine-ind uced vasoconstriction. The purpose of this study was to determine the importance of this interaction between NO and norepinephrine in long-t erm control of renal hemodynamics and arterial pressure. To achieve th is goal, we examined the effects of an intrarenal infusion of norepine phrine (NE) (0.1 mu g . kg(-1). min(-1)) for 7 days in conscious, chro nically instrumented control dogs and in dogs pretreated with a synthe sis inhibitor, L-NAME (3 mu g . kg(-1). min(-1) intrarenally). Both gr oups of dogs also received captopril (15 mu g . kg(-1). min(-1)) plus angiotensin II intravenously to clamp the renin-angiotensin system thr oughout 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) w hile having no effect on mean arterial pressure (100 +/- 3 to 98 +/- 4 mm Hg). In marked contrast, in dogs pre treated with intrarenal L-NAM E (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 i mportant role in modulating the long-term actions of NE on renal funct ion and arterial pressure.