Renal organic cation transporters inhibition affects dopamine-dependent natriuresis and diuresis

KOUYOUMDZIAN NM; RUKAVINA MIKUSIC NL; GORZALCZANY S; CARRANZA A; PANDOLFO M; KRAVETZ MC; FERNÁNDEZ BE; CHOI MR

Buenos Aires

Simposio; International Symposium/Workshop: Renal regulation of blood pressure. Role of angiotensin and dopamine; 2012

American Physiological Society’s Latin American Initiative

Objective: our aim was to demonstrate in vivo whether specific blockadeof organic cation transporters (OCTs) with D-22 and D-24 could inhibit natriuretic and diuretic responsesof exogenous dopamine (DA) administration. Methods: Anesthetized male Sprague Dawleyrats were infused via femoral vein with isotonicsaline (control (C)) plus drug (experimental) for 2 h. Groups:C, carbidopa (CB) alone (an endogenous inhibitor of DA synthesis, 200 mg/kg i.p. 24 and 2 h before treatment); CB+D-22 or D-24; CB+DA alone or with D-22 or D24. Mean arterial pressure, heart rate, creatinine clearence, urine output, fractional and urinary sodium excretion (FENa and uNa.V respectively) were assessed. Results: At 90 and 120 minutes: Diuresis (ml/min±SEM): C: 7,9±1,0 and 6,8±0,9; CB: 6,0±1,1 and 5,5±1,0; CB+DA(100 mg/kg/hr): 20,7±3,4* and 21,5±3,2*; CB+D-22(10 mg/kg/hr): 6,5±0,9 and 5,7±0,9; CB+DA+D-22: 8,0±1,3# and 8,3±1,4#; CB+D-24(10 mg/kg/hr): 6,6±1,2 and 5,3±1,1; CB+DA+D-24: 9,0±2,0# and 8,6±1,8#. FENa (%±SEM): C: 0,26±0,08 and 0,19±0,05; CB: 0,18±0,06 and 0,14±0,05; CB+DA: 1,31±0,11* and 1,42±0,18*; CB+D-22: 0,17±0,05 and 0,12±0,07; CB+DA+D-22: 0,35±0,08** and 0,36±0,09**; CB+D-24: 0,16±0,08 and 0,13±0,06; CB+DA+D-24: 0,38±0,06** and 0,34±0,05**. uNa.V (mEq/min±SEM): C: 0,81±0,19 and 0,55±0,12; CB: 0,60±0,08 and 0,43±0,09; CB+DA: 3,80±0,4* and 4,10±0,5*; CB+D-22: 0,62±0,11 and 0,45±0,11;  CB+DA+D-22: 1,30±0,12** and 1,40±0,1**; CB+D-24: 0,58±0,09 and 0,42±0,06; CB+DA+D-24: 1,40±0,09** and 1,30±0,08**. *p<0,01 vs CB; **p<0,01 vs CB+DA; #p<0.05 vs CB+DA. n= 6-9, Tukey test and ANOVA. Conclusions: Under CB pretreatment, the specific blockers D-22 and D-24 inhibit DA tubular effects, demonstrating that OCTs are responsable of renal DA tubular uptake and therefore of its diuretic and natriuretic actions.