Vasopressin increases glomerular filtration rate in conscious rats through its antidiuretic action

To evaluate the possible influence of chronic alterations in urine concentrating activity (CA) on renal hemodynamics, adult male Sprague-Dawley rats were submitted for 7 days to one of three different levels of CA. CA was either reduced by increasing water intake (mixing the food with a gel bringing 1.6 mL water per g food) (Low-CA), or increased by chronic intraperitoneal infusion of 1-desamino 8-D-arginine vasopressin (200 ng/day) (High-CA). Low-CA, High-CA, and control rats were housed in metabolic cages, ate the same quantity of dry food (the amount provided being slightly lower than the spontaneous intake), and had free access to drinking water. The only difference between groups thus concerned the water intake-vasopressin axis. Radiolabeled (14C)inulin was infused chronically by osmotic minipumps. Urine was collected during Days 5, 6, and 7, and blood samples were taken for determination of plasma composition (P), absolute and fractional (FE) urinary excretion, and clearance (C) of inulin, creatinine, urea, and main electrolytes. This protocol produced mean 24-h urine osmolality (Uosm) ranging from 500 to 3500 mosmol/kg H2O without inducing any disturbance in body fluids or plasma osmolality (Posm). Results show that GFR (Cinulin) was markedly and positively correlated with Uosm (r = 0.798, P < 0.001) and free water reabsorption (r = 0.819, P < 0.001). For Uosm = 2500 mosm/kg H2O, GFR was 47% higher than for Uosm = 500 mosm/kg H2O. Ccreat underestimated GFR in High-CA and overestimated it in Low-CA. FEurea was inversely related to Uosm, as expected from the increased reabsorption known to occur at low urine flows. It is tentatively proposed that the intrarenal recycling of urea, triggered by vasopressin and essential to the urinary concentrating mechanism, might influence GFR indirectly by modifying the composition of the tubular fluid at the macula densa and thus the intensity of the tubuloglomerular feedback control of GFR. Even if this mechanism remains to be confirmed, this study unequivocally demonstrates, in normal conscious rats, that the level of urinary concentrating activity has a major influence on basal GFR.