Evaluation of a low dose of Angiotensin II infusion as regulator of renal dopaminergic system through organic cation transporters

KOUYOUMDZIAN NM; RUKAVINA MIKUSIC NL; ROBBESAUL GD; ALVAREZ PRIMO M; GORZALCZANY S; PANDOLFO M; GIRONACCI MM; ROSON MI; TOBLLI JE; FERNÁNDEZ BE; CHOI MR

Ciudad Autónoma de Buenos Aires

Congreso; LXII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2017

Sociedad Argentina de Investigación Clínica (SAIC)

Abstract: Theaim of this study was to evaluate the effects of a low dose of angiotensin II(ANG II: 1 ug/kg/hour) on renal dopaminergis system (RDS) through determinationof the organic cation transporters (OCTs and OCTNs) expression in renal cortex,dopamine (DA) urinary levels, Na+,K+?ATPasa (NKA) activity and renal function.Under inhibition of DA synthesis by benserazide, anesthetized male SpragueDawley rats were infused with isotonic saline solution during 120 minutes andrandomized in nine different groups: control, pargyline plus tolcapone (P+T),ANG II, DA, ANG II+DA, D-22, ANG II+D-22, DA+D-22 and ANG II+DA+D-22. Renalfunctional parameters and direct blood pressure were determined and urinary DAconcentration was quantified by HPLC. Expression of OCTs, OCTNs, D1-subtypereceptor (D1R) and NKA in membrane preparations from renal cortex tissues weredetermined by Western Blot. NKA activity was determined using in vitro enzymeassay. Compared to P+T group, DA infusion significantly increased fractionalexcretion of sodium (FENa) and DA excretion (*: p<0,05). These effects werenot observed with ANG II infusion except in ANG II+DA group versus DA group forFENa values after 120 minutes of infusion (*). OCTs blockade by D-22, reversedDA-dependent natriuresis demonstrating that OCTs are implied in DA uptake andtransport in renal tissues. The activity of NKA was greater in ANG II groupsversus respective animals without ANG II (*). OCTs, D1R, NKA and phosphorilatedNKA protein expression were not modified by ANG II infusion. Urinary DAconcentration was not altered in ANG II+DA rats versus DA alone group. Thisresult is consistent with the fact that total OCTNs expression was not affectedby ANG II, despite obtaining significant augmentation (*) of OCTN-1 expressionversus P+T rats. To conclude, ANG II modifies the activity of NKA, the finaleffector of DA-D1R pathway, without affecting RDS.