Effects of dopamine and nitric oxide on arterial pressure and renal function in volume expansion

Abstract

Summary: 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.), N^G‐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 (NO_x) 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 NO_x 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.