The present experiment was designed to investigate the role of peripheral dopamine D1-like receptors and to evaluate the prophylactic effect of zelandopam, a dopamine D1-like receptor agonist, on puromycin aminonucleoside (PA)-induced nephrosis in rats. Rats were divided into six groups (n=10 per group): 0.9% saline-injected rats (control); PA-injected rats (PAN); PA-injected rats treated with the selective dopamine D1-like receptor agonist zelandopam (30, 100, 300 mg/kg p.o. twice a day); PA-injected rats treated with prednisolone (1 mg/kg p.o. once a day). Nephrosis was induced in rats with a single intravenous injection of PA at a dose of 50 mg/kg. The effects of zelandopam and prednisolone in PA nephrosis rats were evaluated before injection of PA and at 7 and 14 days after injection. PA-induced nephrosis was characterized by an increase in urinary protein excretion (proteinuria) and plasma total cholesterol. Zelandopam dose-dependently attenuated the increase in proteinuria and total cholesterol. Prednisolone significantly attenuated the increase in proteinuria and total cholesterol and resulted in a significant decrease in body weight. The present study demonstrates for the first time that zelandopam, a selective dopamine D1-like receptor agonist, is effective in blunting the development of PA-induced nephrosis, and that the effects of zelandopam are dose dependent.
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