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Acute infusion of angiotensin II regulates organic cation transporters function in the kidney: its impact on the renal dopaminergic system and sodium excretion

Hypertension Research volume 44, pages 286–298 (2021)Cite this article

Abstract

A close relationship between angiotensin II (ANG II) and the renal dopaminergic system (RDS) has been reported. Our aim was to study whether renal dopamine and ANG II can interact to modify renal sodium handling and then to elucidate the related mechanism. Anesthetized male Sprague–Dawley rats were used in experiments. ANG II, exogenous dopamine, and decynium-22 (or D-22, an isocyanine that specifically blocks electrogenic organic cation transporters, OCTs), were infused in vivo for 120 min. We analyzed renal and hemodynamic parameters, renal Na+, K+-ATPase levels, OCT activity, and urinary dopamine concentrations. We also evaluated the expression of D1 receptor, electroneutral organic cation transporters (OCTNs), and OCTs. ANG II decreased renal excretion of sodium in the presence of exogenous dopamine, increased Na+, K+-ATPase activity, and decreased the urinary dopamine concentration. D-22 treatment exacerbated the ANG II-mediated decrease in renal excretion of sodium and dopamine urine excretion but did not modify ANG II stimulation of Na+, K+-ATPase activity. The infusion of ANG II did not affect the expression of D1 receptor, OCTs, or OCTNs. However, the activity of OCTs was diminished by the presence of ANG II. Although ANG II did not alter the expression of D1 receptor, OCTs, and OCTNs in renal tissues, it modified the activity of OCTs and thereby decreased the urinary dopamine concentration, showing a novel mechanism by which ANG II decreases dopamine transport and its availability in the tubular lumen to stimulate D1 receptor. This study demonstrates a relationship between ANG II and dopamine, where both agents counteract their effects on sodium excretion.

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Acknowledgements

We thank Dr. María C. Kravetz from Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina; Dr. Graciela L. Giardina from Hospital Alemán, Laboratorio de Medicina Experimental, Buenos Aires, Argentina; Dr. Mariela Gironacci from CONICET–Universidad de Buenos Aires, Instituto de Química y Fisicoquímica Biológicas, Buenos Aires, Argentina'; and Dr. Gabriel Cao, Dr. Silvana L. Della Penna, and Dr. María I. Rosón from IATIMET, Buenos Aires, Argentina, for their technical collaboration.

Grants

This work was supported by grants from the ANPCYT (PICT 2012–1775), Universidad de Buenos Aires (UBACYT20020110200048 and 2002013200105BA) and Sociedad Argentina de Hipertensión Arterial (Stimulus Grant for Research on Hypertension 2014–2015) and Instituto Universitario en Ciencias de la Salud, Fundación Héctor A. Barceló (2017–2019).

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Authors and Affiliations

  1. Universidad de Buenos Aires. CONICET, Instituto Alberto C. Taquini de Investigaciones en Medicina Traslacional (IATIMET), Buenos Aires, Argentina

    Nicolás M. Kouyoumdzian, Natalia L. Rukavina Mikusic, Gabriel D. Robbesaul & Marcelo R. Choi

  2. Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Farmacología, Cátedra de Farmacología, Buenos Aires, Argentina

    Susana B. Gorzalczany & Andrea Carranza

  3. Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Bioquímica Clínica, Cátedra de Bioquímica Clínica, Buenos Aires, Argentina

    Verónica Trida

  4. Instituto Universitario de Ciencias de la Salud, Fundación H.A. Barceló, Buenos Aires, Argentina

    Belisario E. Fernández & Marcelo R. Choi

  5. Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Ciencias Biológicas, Cátedra de Anatomía e Histología, Buenos Aires, Argentina

    Marcelo R. Choi

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  1. Nicolás M. Kouyoumdzian
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Contributions

NMK performed all the experiments, analyzed the results, and wrote the manuscript. NLRM performed all the experiments, analyzed the results, and revised the manuscript. GDR collaborated in the surgery of the animals and measured urinary dopamine concentration by HPLC. SBG performed the surgery of all the animals and measured the mean arterial pressure. AC collaborated in western blot analyses. VT measured urine and plasma parameters. BEF analyzed the results and collaborated with manuscript writing and revision. MRC analyzed immunohistochemistry images, planned and directed the project, procured funding, and revised manuscript writing.

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Correspondence to Nicolás M. Kouyoumdzian.

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In memory of Dr. Jorge E. Toblli who passed away before the submission of the manuscript.

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Kouyoumdzian, N.M., Rukavina Mikusic, N.L., Robbesaul, G.D. et al. Acute infusion of angiotensin II regulates organic cation transporters function in the kidney: its impact on the renal dopaminergic system and sodium excretion. Hypertens Res 44, 286–298 (2021). https://doi.org/10.1038/s41440-020-00552-7

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