Isotonic volume expansion in rats role of renal dopamine and Mao activity to regulate hydroelectrolitic excretion

V DE LUCA SAROBE, LA DI CIANO, G LEVIN, EE ARRIZURIETA, FR IBARRA

Rio de Janeiro, Brasil

Congreso; World Congress of Nephrology; 2007

International Society of Nephrology

The role of dopamine  (DA) degrading enzymes, MAO and COMT, regarding intrarenal dopamine effects and hydroelectrolyte excretion is controversial. In conscious rats, we have reported that MAO inhibition increases urinary DA but it does not modify natriuresis, quite opposite to COMT inhibition (Pfl Arch 450, 2005). To test the hypothesis whether MAO could be involved, via intrarenal DA, as a regulator of the diuresis observed in volume expansion, male Wistar rats (bwt 250-300g) were used. After suitable preparation rats received a moderate isotonic volume expansion with saline (NaCl 0.9%) at a rate of 5% bwt per hour. Three groups were explored: expansion (controls), expansion plus MAO inhibitor Pargyline (20 mg/kg bwt, i.v.) (IMAO) and expansion plus COMT inhibitor 3-4-Dinitrocatechol (15 mg/kg bwt, i.v.) (ICOMT). Experiments were run in parallel. After , control rats under expansion showed an increment in diuresis (µl/min/100g bwt) and natriuresis (µmol/min/100g bwt) from 1.77±0.06 to 30.58±5.58* and 0.53±0.4 to 4.75±1.05* (p<0.01, both), respectively. Mean arterial pressure (MAP) was 123±2.1 mmHg and was unchanged by volume expansion. Inulin clearance (CIN, ml/min/100g bwt) increased during expansion from 0.59±0.04 to 0.73±0.04* (p<0.05). In control rats basal MAO activity was (nmol/mg tissue/hr) 7.66±0.52 in renal cortex and 3.16±0.40 in medulla. After expansion MAO decreased to 5.65±0.72* in cortex and to 2.3±0.6 in medulla (p<0.05). Urinary DA excretion (ng/min/100g bwt) increased after expansion from basal value 0.12±0.012 to 0.29±0.04* (p<0.05). IMAO rats showed a diuresis and natriuresis over 50% of controls, to 44.92±1.11** and 6.77±0.90** (p<0.05), respectively. Neither MAP nor CIN were modified by IMAO as compared with controls. Urinary DA excretion significantly increased over controls after IMAO to 0.43±0.05** (p<0.05). MAO activity was completely abolished by Pargyline. Treatment with D1 receptor antagonist SCH 23390 3µg/kg bwt reduced the diuretic and natriuretic response by more than 50% in IMAO and control rats. In ICOMT rats no changes were observed either in hydroelectrolyte excretion or in hemodynamic variables compared with controls. The increase in hydroelectrolyte excretion during isotonic volume expansion is under MAO regulation, since it is enhanced by MAO inhibition and depends on a higher endogenous DA.