In seven healthy, young subjects on a 240 mmol sodium diet, mean arterial pressure (MAP), renal hemodynamics, and renal handling of Na and exogenous Li were measured at baseline and during short-term nitric oxide (NO) blockade with a 90-minute infusion of 3.0 microg x kg(-1) x min(-1) of N(G)-L-arginine methyl ester (L-NAME). The infusion was performed twice: after a 3-day pretreatment with either placebo or 50 mg losartan to block Ang II receptors. With placebo, L-NAME produced no change in MAP from 0 to 45 minutes (period 1) and only a 5% increase at 45 to 90 minutes (period 2) of infusion. Effective renal plasma flow (ERPF, PAH clearance) and glomerular filtration rate (GFR, inulin clearance) declined by 11.7% and 8.0%, respectively in period 1 and by 14.6% and 11.6%, respectively, in period 2. Calculated renal vascular resistance (RVR) increased by 13.0% to 20.6%. Fractional excretion of Na (FE(Na)) and Li (FE(Li)) fell by 30.0% and 21.0%, respectively, in period 1 and by 44.2% and 31.1% in period 2. All these variations were significant versus baseline. With losartan, the rise in MAP at 45 to 90 minutes was completely abolished, whereas all changes in ERPF, GFR, RVR, FE(Na), and FE(Li) in response to L-NAME were the same as those observed with placebo. The present data show that NO blockade with low-dose systemic infusion of L-NAME produces renal vasoconstriction, reduced GFR, and increased tubular Na reabsorption independent of changes in MAP. Reduced FE(Li) indicates an effect of NO on the proximal tubule. Since these changes are not prevented by losartan, we conclude that in Na-repleted humans, renal vasoconstriction and Na-retaining effects of inhibition of basal NO production are not due to the unopposed action of endogenous Ang II.

Abstract-In eight young healthy subjects on a 240 mM Na diet mean arterial pressure (MAP), renal hemodynamlcs and renal handling of Na and exogenous Ll were measured at baseline and durmg acute nitric oxide (NO) mhlbltlon with 90-minute mfuslon of 3 Opg/kg mm-' of NC-L-argmme methyl ester (L-NAME) The same experiment was repeated with mfuslon of 50pg/kg mm-' of DA, receptor blocker L-Sulpmde (L-SULP) alone and, finally, with simultaneous mfuslon of both L-NAME and L-SULP L-SULP alone did not elicit any effect L-NAME alone produced no changes m MAP from 0 to 45 minutes (PJ and a 6 6% increase at 45 to 90 minutes (P2) of mfuslon Effective renal plasma flow (ERPF, PAH clearance) and glomerular filtration rate (GFR, muhn clearance) declined by 10 2% and 7 6%, respectively, m P, and by 15 3% and 11 5% m P, Flltratlon Fraction (FF) rose by 4 2% m Pz Calculated renal vascular resistance (RVR) increased by 13 0% to 25.6% Fractional excretion of Na (FENa) and L1 (FEL1) fell by 20 0% and by 16.0%, respectively, m P, and by 40 0% and 25 1% m Pz All these vanatlons, except for MAP and GFR, were slgmficantly greater during comfuslon of L-NAME and L-SULP ERPF declined by 17 8% to 33 7%, FENa by 26 7% to 53 3%, FELl by 13 8% to 34 8%, while RVR rose by 22 5% to 59 1% and FF by 10 1% to 29 3% The present data confirm that NO blockade with low-dose systemic mfuslon of L-NAME produces renal vasoconstnctlon, reduced GFR with slight increase m FF, and enhanced tubular Ll, and Na reabsorption Since increase m RVR and FF and decrease m FENa and FELl are markedly potentlated by the simultaneous mfuslon of DA2 blocker L-SULP, which exerts no effects by Itself, we suggest that DA mteractlons between DA system at the level of DA2 receptors and basal NO production play a physlologlcal role m the regulation of renal function m humans (Hypertension, 1998;31[part2]:277-282.)Key Words: DA2 receptor n L-SULP n L-NAME n human n kidney n mtnc oxide n hemodynamlcs T he endogenous cathecolamme dopamme (DA) 1s involved m a wide variety of physlologlcal processes and contributes to modulation of many functions including behavior, movement, nerve conduction, hormone synthesis and release, blood pressure and renal hemodynamlcs, and sodium handling Outside of the central nervous system, DA receptors have been divided on the basis of their locahsatlon into two maJor groups, the presynaptlc (DA,) and postsynaptlc (DA,) subtypes 1~23 Wlthm the kidney, DA, receptors have been localized postsynaptlcally m blood vessels, proximal convoluted tubule, and collectmg duct 133 Increase m ademlcyclase actlvlty, renal vasodllatlon and natnurens, mhlbltable by DA, antagorusts, are known to follow DA, receptor stlmulatlon by infusion of DA or specific DA, agomstlc drugs 1~ DA, receptors have been identified presynaptlcally on sympathetic nerve termmals m the adventltla of the renal vasculature I,* 7 Due to their preJunctlona1 locahsatlon, DA2 receptor actlvatlon 1s thought to mhlblt at that level the NE release thus modulatmg RSNA ',*s3 The physlologcal role of presyn...

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