title: Enhanced sodium retention after acute nitric oxide blockade in mildly sodium loaded patients with essential hypertension.
abstract: In essential hypertension (ESS) whole body and vascular nitric oxide (NO) synthesis is generally thought to be reduced. We therefore investigated the systemic and renal responses to acute treatment with N(G)-monomethyl-l-arginine (L-NMMA), a competitive NOS-inhibitor, in 12 patients with ESS and 18 healthy controls (CON) in a randomized, placebo-controlled study. Main effect parameters were renal hemodynamics (glomerular filtration rate [GFR] and renal plasma flow [RPF]), systemic blood pressure (BP), and fractional excretions of sodium (FE(Na)) and lithium (FE(Li)). Experiments were performed on two occasions for each subject studying the effects of either L-NMMA (3 mg/kg intravenously) or placebo. The patients with ESS were studied after at least 14 days off antihypertensive medication. Renal hemodynamics were assessed by the clearances of (125)I-hippuran (RPF) and (51)Cr-EDTA (GFR). The L-NMMA induced a significant increase in systemic BP and significant reductions in RPF, FE(Na), and FE(Li) in both groups. The increase in diastolic BP was significantly attenuated in ESS (ESS: 8% +/- 2% v CON: 14% +/- 2%, P < .05). The GFR and RPF were equally reduced by L-NMMA in both groups (RPF(ESS): -19% +/- 4% v RPF(CON): -15% +/- 3%, P = not significant [NS]). However, the reduction in FE(Na) was enhanced in ESS (ESS: -42% +/- 7% v CON: -25% +/- 3%, P < .01). The FE(Li) decreased equally in both groups (ESS: -17% +/- 2% v CON: -17% +/- 6%, P = NS). It is concluded that acute NO blockade in ESS is accompanied by a reduced systemic pressor response, an unchanged renal hemodynamic response, and an enhanced reduction in FE(Na). The results suggest that patients with essential hypertension are highly dependent on NO to maintain sodium excretion.
authors.affiliation: Department of Medical Research, Holstebro Hospital, Aalborg Hospital and Aarhus University, Aarhus, Denmark. jnbech@dadlnet.dk
authors.forename: Jesper N
authors.initials: JN
authors.lastname: Bech
authors.forename: Eigil H
authors.initials: EH
authors.lastname: Nielsen
authors.forename: Robert S
authors.initials: RS
authors.lastname: Pedersen
authors.forename: Kristina B
authors.initials: KB
authors.lastname: Svendsen
authors.forename: Erling B
authors.initials: EB
authors.lastname: Pedersen
mesh_terms: D000284:Administration, Oral; D000328:Adult; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D006152:Cyclic GMP / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology / Q000652:urine; D008094:Lithium / Q000652:urine; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects*; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012079:Renal Circulation / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects; D012964:Sodium / Q000652:urine; D012965:Sodium Chloride / Q000008:administration & dosage / Q000378:metabolism*; D013997:Time Factors; D019323:omega-N-Methylarginine / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D020097:Natriuretic Peptide, Brain; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D012965:Sodium Chloride; D009320:Atrial Natriuretic Factor; D008094:Lithium; D012964:Sodium; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP