Effects OfL-Arginine And Furosemide On Blood Pressure And Renal Function In Volume-Expanded Rats

Authors: Costa, Ma1; Marchetti, M1; Balaszczuk, Am1; Arranz, Ct1

Source: Clinical and Experimental Pharmacology and Physiology, Volume 28, Number 7, July 2001 , pp. 528-532(5)

Publisher: Blackwell Publishing

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Abstract:

SUMMARY

1. The aim of the present study was to investigate the effects ofL-arginine (L-Arg) on blood pressure and water and electrolyte excretion in control and extracellular fluid volume-expanded rats (10% bodyweight with 0.9% NaCl) and to determine whether diuretic treatment with furosemide (FUR) can be optimized by the administration ofL-Arg in this model.

2. Both groups of animals were anaesthetized, divided into groups and treated with either 7.5 mg/kg FUR, 250 mg/kgL-Arg, 1 mg/kg NG-nitro-L-arginine methyl ester (L-NAME), FUR +L-NAME or FUR +L-Arg. Mean arterial pressure (MAP), diuresis, natriuresis and kaliuresis were determined.

3. Extracellular fluid volume expansion induced no changes in MAP in control and volume-expanded rats (92±6 vs 100±8 mmHg, respectively). The hypotension induced by FUR in control and volume-expanded rats (69±7 and 76±5 mmHg, respectively) was significantly (P < 0.01) enhanced by the administration ofL-Arg (54±3 and 64±3 mmHg, respectively).

4. Injection ofL-NAME increased MAP and diminished diuresis, natriuresis and kaliuresis in both groups.

5. Furosemide-induced water and electrolyte excretion was blunted by the administration ofL-NAME.

6. The combination ofL-Arg + FUR increased diuresis induced by FUR alone (control rats: 29.33±1.68 vs 12.91± 0.41 μL/min per 100 g, respectively; volume-expanded rats: 248.5±25.4 vs 112,6±8.3 μL/min per 100 g, respectively; P < 0.01).

7. The administration of the combination ofL-Arg + FUR promoted a decrease in the sodium/water excretion ratio compared with the administration of FUR alone (control rats: 0.230±0.018 vs 0.45±0.03, respectively, P < 0.001; volume-expanded rats: 0.091±0.010 vs 0.22±0.03, respectively, P < 0.01).

8. The potassium/water excretion rate induced by FUR alone and in the presence ofL-Arg followed a pattern similar to that seen for natriuresis (control rats: 0.35±0.05 vs 0.20±0.05 μEq/min per 100 g, respectively; volume-expanded rats: 0.045±0.008 vs 0.014±0.003 μEq/min per 100 g, respectively; P < 0.01).

9. The decrease in the electrolyte/water excretion ratio observed with FUR +L-Arg in volume-expanded rats was greater than in control animals.

10. The results of the present study show that the administration of FUR withL-Arg contributes to enhanced hypotensive and diuretic effects of FUR, thus diminishing the relative electrolyte excretion in normal conditions and in extracellular fluid volume expansion.

Keywords: L-arginine; arterial blood pressure; extracellular fluid volume expansion; furosemide; nitric oxide; rat; renal function

Document Type: Research article

DOI: 10.1046/j.1440-1681.2001.03482.x

Affiliations: 1: Cátedra de Fisiología, Departamento de Ciencias Biológicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires and

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