Effects of dopamine and nitric oxide on arterial pressure and renal function in volume expansion.
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 microL/min per 100 g; P < 0.01) and expanded animals (24.42 +/- 3.67 vs 17.85 +/- 2.16 microL/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 microL/min per 100 g; P < 0.01) and expanded animals (44.26 +/- 8.45 vs 25.43 +/- 5.12 microL/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 microEq/min per 100 g; P < 0.01) and expanded animals (3.72 +/- 0.70 vs 1.89 +/- 0.23 microEq/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 microEq/min per 100 g; P < 0.01) and expanded rats (12.77 +/- 0.05 vs 3.53 +/- 0.75 microEq/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.
Costa
Maria de los Angeles
Mde L
Cátedra de Fisiología, Departamento de Ciencias Biológicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina. mcosta@huemul.ffyb.uba.ar
Loria
A
A
Marchetti
M
M
Balaszczuk
A M
AM
Arranz
C T
CT
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D001810:Blood Volume / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D005110:Extracellular Space / Q000187:drug effects / Q000502:physiology*; D006220:Haloperidol / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D007677:Kidney Function Tests / Q000379:methods; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D009569:Nitric Oxide; D001120:Arginine; D006220:Haloperidol; D019331:NG-Nitroarginine Methyl Ester; D004298:Dopamine