Abstract 275: The Effect of High Salt-diet on Pioglitazone Treated-db/db-/- mice

Abstract

The objective of this study was to evaluate the impact of high-salt-diet on pioglitazone treated db/db mice. Groups of 6 weeks-old db/db mice obtained from Jackson Laboratory were given either pioglitazone (0.02%) in diet or pioglitazone (0.02%) plus high salt-diet (8% NaCl) for 6 to 12 weeks. Control groups received either pioglitazone or normal salt diet. During the course of treatment, urine volume, urine sodium, creatinine and blood glucose were measured in the animals. For urine collection, mice were placed in metabolic cages. In order to evaluate whether differences exist between diabetic animals that received pioglitazone or not in the handling of a sodium load and to characterize the transport mechanisms involved, at the end of experimental period the animals were given an acute sodium load (physiological saline), 1.25 ml/100 g body weight by intraperitoneal route. The sodium load was repeated in mice that was treated 15 minutes earlier with hydrochlorothiazide (40 mg/kg i.p.) or furosemide (8 mg/kg i.p.), or amiloride (1.65 mg/kg). The animals were placed in metabolic cages and urine voided was collected over 5 hr. for determination of urine volume and sodium. Sodium was determined by flame photometer. No significant changes were observed in mean arterial blood pressure in all the groups (at p 0.05). There was significant increase in UNav with all the diuretics in db/db mice that received high salt diet at 6 weeks. The blood pressure did not increase with the sodium diet. This might be due to natriuresis resulting from polyurea in the diabetic condition of the mice.