Angiotensin II blockade does not prevent renal effects of L-NAME in sodium-repleted humans.
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.
Montanari
A
A
Istituto di Patologia Medica, University of Parma, Italy. montalbr@ipruniv.cce.unipr.it
Tateo
E
E
Fasoli
E
E
Giberti
D
D
Perinotto
P
P
Novarini
A
A
Dall'Aglio
P
P
D000328:Adult; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D019808:Losartan; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D012982:Sodium, Dietary / Q000008:administration & dosage*; D013777:Tetrazoles / Q000494:pharmacology*
D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors; D007093:Imidazoles; D012982:Sodium, Dietary; D013777:Tetrazoles; D000804:Angiotensin II; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester