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BioMed Research International
Volume 2013 (2013), Article ID 397391, 8 pages
http://dx.doi.org/10.1155/2013/397391
Research Article

Concerted Action of ANP and Dopamine D1-Receptor to Regulate Sodium Homeostasis in Nephrotic Syndrome

1Nephrology Research & Development Unit, Faculty of Medicine, University of Porto & Hospital S. João EPE, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
2Faculty of Dental Medicine, University of Porto, Rua Dr. Manuel Pereira da Silva, 4200-393 Porto, Portugal
3Laboratory of General Physiology, Unit for Multidisciplinary Biomedical Research (UMIB), Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Rua de Jorge Viterbo Ferreira No. 228, 4050-313 Porto, Portugal
4Renal y Cardiovascular Physiopathology Research Unit, Instituto Reina Sofia de Investigación Nefrológica, Department of Physiology and Pharmacology, University of Salamanca, Edificio Departamental S-20 Campus Miguel de Unamuno, 37007 Salamanca, Spain
5Instituto de Estudios de Ciencias de la Salud de Castilla y León (IECSCYL), Research Unit, University Hospital of Salamanca, Paseo de San Vicente 58-182, 37007 Salamanca, Spain

Received 25 April 2013; Revised 23 June 2013; Accepted 24 June 2013

Academic Editor: Dimitrios P. Bogdanos

Copyright © 2013 Cátia Fernandes-Cerqueira et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The edema formation in nephrotic syndrome (NS) is associated with a blunted response to atrial natriuretic peptide (ANP). The natriuretic effects of ANP have been related to renal dopamine D1-receptors (D1R). We examined the interaction between ANP and renal D1R in rats with puromycin aminonucleoside-induced NS (PAN-NS). Urinary sodium, cyclic guanosine monophosphate (cGMP) excretion, and D1R protein expression and localization in renal tubules were evaluated in PAN-NS and control rats before and during volume expansion (VE). The effects of zaprinast (phosphodiesterase type 5 inhibitor), alone or in combination with Sch-23390 (D1R antagonist), were examined in both groups. The increased natriuresis and urinary cGMP excretion evoked by acute VE were blunted in PAN-NS despite increased levels of circulating ANP. This was accompanied in PAN-NS by a marked decrease of D1R expression in the renal tubules. Infusion of zaprinast in PAN-NS resulted in increased urinary excretion of cGMP and sodium to similar levels of control rats and increased expression of D1R in the plasma membrane of renal tubular cells. Combined administration of Sch-23390 and zaprinast prevented natriuresis and increased cGMP excretion induced by zaprinast alone. We conclude that D1R may play a major role in the ANP resistance observed in PAN-NS.