title: Concerted action of ANP and dopamine D1-receptor to regulate sodium homeostasis in nephrotic syndrome.
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.
authors: Nephrology Research & Development Unit, Faculty of Medicine, University of Porto & Hospital S. João EPE, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.
authors: Cátia
authors: C
authors: Fernandes-Cerqueira
authors: Benedita
authors: B
authors: Sampaio-Maia
authors: Janete
authors: J
authors: Quelhas-Santos
authors: Mónica
authors: M
authors: Moreira-Rodrigues
authors: Liliana
authors: L
authors: Simões-Silva
authors: Ana M
authors: AM
authors: Blazquez-Medela
authors: C
authors: C
authors: Martinez-Salgado
authors: Jose M
authors: JM
authors: Lopez-Novoa
authors: Manuel
authors: M
authors: Pestana
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001552:Benzazepines / Q000008:administration & dosage; D006152:Cyclic GMP / Q000652:urine; D005919:Glomerular Filtration Rate; D006706:Homeostasis; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D009404:Nephrotic Syndrome / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D011688:Purinones / Q000008:administration & dosage; D011692:Puromycin Aminonucleoside / Q000633:toxicity; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*
chemical_list: D001552:Benzazepines; D011688:Purinones; D017447:Receptors, Dopamine D1; C534628:SCH 23390; D011692:Puromycin Aminonucleoside; D009320:Atrial Natriuretic Factor; D012964:Sodium; C011145:zaprinast; D006152:Cyclic GMP
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