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Notes: 1. The aim of the present study was to investigate the role of dopamine (DA) in the hypotensive and renal effects of l-arginine during extracellular fluid volume expansion (10% bodyweight).2. Animals were randomized to non-expanded and expanded groups. Both groups received different treatments: l-arginine (250 mg/kg, i.v.), NG-nitro-l-arginine methyl ester (l-NAME; 1 mg/kg, i.v.), haloperidol (3 mg/kg, i.p.) and l-arginine + haloperidol (n = 8). Mean arterial pressure (MAP), diuresis, natriuresis, kaliuresis, glomerular filtration rate, renal plasma flow (RPF) and nitrite and nitrate (NOx) excretion were determined.3. The increase in MAP induced by l-NAME was greater in expanded than in non-expanded rats (42 ± 3 vs 32 ± 3 mmHg, respectively; P 〈 0.01). Administration of haloperidol did not modify the l-arginine hypotensive effect.4. Blockade of nitric oxide synthase diminished urine flow in non-expanded (4.15 ± 0.56 vs 0.55 ± 0.11 µL/min per 100 g; P 〈 0.01) and expanded animals (24.42 ± 3.67 vs 17.85 ± 2.16 µL/min per 100 g; P 〈 0.01). Diuresis induced by l-arginine was reduced by DA blockade in both non-expanded (17.15 ± 2.11 vs 6.82 ± 0.61 µL/min per 100 g; P 〈 0.01) and expanded animals (44.26 ± 8.45 vs 25.43 ± 5.12 µL/min per 100 g; P 〈 0.01).5. Sodium excretion decreased with l-NAME treatment in non-expanded (0.22 ± 0.03 vs 0.06 ± 0.01 µEq/min per 100 g; P 〈 0.01) and expanded animals (3.72 ± 0.70 vs 1.89 ± 0.23 µEq/min per 100 g; P 〈 0.01). Natriuresis induced by l-arginine was diminished by haloperidol both in non-expanded (0.94 ± 0.13 vs 0.43 ± 0.04 µEq/min per 100 g; P 〈 0.01) and expanded rats (12.77 ± 0.05 vs 3.53 ± 0.75 µEq/min per 100 g; P 〈 0.01). Changes in kaliuresis changes seen following treatment with l-arginine, l-NAME and l-arginine + haloperidol followed a pattern similar to that observed for sodium excretion in both groups of rats.6. l-Arginine enhanced RPF in non-expanded animals (11.96 ± 0.81 vs 14.52 ± 1.05 mL/min per 100 g; P 〈 0.01). Glomerular filtration rate was increased by extracellular volume expansion (3.08 ± 0.28 vs 5.42 ± 0.46 mL/min per 100 g; P 〈 0.01).7. The increase in NOx induced by acute volume expansion (0.18 ± 0.03 vs 0.52 ± 0.08 nmol/min per 100 g; P 〈 0.01) was diminished following the administration of haloperidol (0.52 ± 0.08 vs 0.26 ± 0.06 nmol/min per 100 g; P 〈 0.01).8. Although DA does not participate in the actions of nitric oxide on vascular tone, both systems would play an important role in renal function adaptation during extracellular fluid volume expansion.

Notes: 1. The aim of the present study was to investigate the effects of L-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 of L-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/kg L-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 of L-Arg (54±3 and 64±3 mmHg, respectively).4. Injection of L-NAME increased MAP and diminished diuresis, natriuresis and kaliuresis in both groups.5. Furosemide-induced water and electrolyte excretion was blunted by the administration of L-NAME.6. The combination of L-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 of L-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 of L-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 with L-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.