The effect of mannitol on antidiuretic and natriuretic actions of ADH in rats

The effect of mannitol and glucose on antidiuretic and natriuretic actions of ADH was investigated in water-loaded, male Sprague-Dawley rats anesthetized with sodium pentobarbital (5 mg/100g). Water diuresis was induced and sustained by continuous intravenous perfusion of hypotonic solution containing 0.3% NaCl, 1.67% glucose, 1.2% ethanol and sufficient inulin at a constant rate 150 microliters/min. Arginine vasopressin at a single dose 0.1 ng/100g was tested twice in the phase of water diuresis and in the phase of water diuresis plus mannitol osmotic diuresis. Urine samples were collected at ten-minute intervals. Three doses of mannitol (5.18, 3.63, 1.81 mumol/min/100g) were given into the right renal artery in three groups of experimental rats, respectively. Administration of mannitol did not alter renal inulin clearance but increased urine flow and excretion of sodium from experimental kidney. Our findings show that mannitol reduced antidiuretic response to ADH in the experimental kidney. This reduction was related to intraarterial mannitol doses. Local administration of mannitol increased natriuretic action of ADH in the experimental kidney. However, a small dose (1.81 mumol/min/100g) of mannitol did not increase natriuretic action of ADH. Saline and glucose (5.23 mumol/min/100g) were also infused intra-arterially to replace mannitol. The effect of saline on antidiuretic and natriuretic responses to ADH was found to be insignificant. Glucose reduced antidiuretic response to ADH as mannitol did but failed to alter natriuretic response to ADH as saline did. We conclude that mannitol does positively affect antidiuretic and natriuretic actions of ADH. Glucose has similar effect but much less than mannitol.