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Mechanism of Naproxen-Induced Antidiuretic Response in Dog

This study was attempted to investigate the mechanism of retention of sodium and water by naproxen which is a drug among nonsteroidal anti-inflatnmatory drugs in dogs. Napoxen, when given intravenously in doses ranging from 30mg to 100mg/kg, elicited antidiuresis accompanied with the decrease of osmolar clearance(Cosm) and amounts of sodium excreted in urine(ENa), with the increase of sodium reabsorption rate in renal tubule(RNa) and ratio of potassium against sodium (K/Na). Naproxen infused into a renal artery in doses ranging from 1.Omg to 3.Omg/kg/min produced both diuretic action in infused kidney and antidiuretic action in control kidney. Naproxen injected into carotid artery in doses ranging from 1O.Omg to 30.Omg/kg exhibited antidiuretic action. Changes of renal function in the circumstances of above two antidiuresis were the same with aspect of intravenous naproxen. Antidiuretic action of naproxen injected into carotid artery was not affected by renal denervation, was blocked by pretreatment with i.v. arachidonic acid, prostaglandin precursor, or i.v. indomethacin, cyclooxygenase inhibitor. Naproxen injected into carotid artery abolished the diuretic action of i.v. spironolactone, aldosterone antagonist, and i.v. spironolactone blocked the antidiuretic action of naproxen given into carotid artery. The results suggest that naproxen produced antidiuresis, and sodium and water retention through the central system, the mechanism being related to the prostaglandin biosynthetic inhibition and aldosterone like action.