The possibility that an alteration of the vasopressin-dependent cyclic AMP system plays a pathogenic role in the urinary concentrating defect in K+ depletion was investigated in the rat. The antidiuretic response to vasopressin was significantly less in K+-depleted rats. In these K+-depleted rats, the increase in urinary cyclic AMP excretion in response to vasopressin was also significantly less. However, repletion of K+ for 1 wk by feeding high-K+ diets restored the ability to increase urinary cyclic AMP excretion in response to vasopressin. In the in vitro incubation of renal medullary slices, the increase in cyclic AMP concentration in response to vasopressin was also significantly less in the slices obtained from K+-depleted rats than in those obtained from control rats. These findings suggest that, in K+ depletion, there is a reversible impairment of the vasopressin-dependent cyclic AMP system in the renal medulla; this impairment may play a pathogenic role in the urinary concentrating defect in K+ depletion.

These experiments were designed to evaluate the hypothesis that K+ deficiency may be associated with decreased delivery of urea to the renal papillary collecting duct and/or decreased reabsorption of urea from the papillary collecting duct. Either of these factors would result in diminished capacity for urea recycling and might explain the mechanism of the urinary concentrating defect that is observed in K+ depletion. Munich-Wistar rats were fed 25 ml of water and 12 g of normal (CON) or K'deficient (KD) diet each day for 21 days. Papillary collecting duct samples were obtained by micropuncture through the intact ureter. Fractional delivery of H 2 0 to the base and tip of the papillary collecting duct was increased in KD as compared to CON rats (1 S O f 0.30% in KD vs 0.72 2 0.09% in CON at the base, P < 0.01; and 0.55 k 0.08% in KD vs 0.30 k 0.05% in CON at the tip, P < 0.01). However, fractional delivery of urea to the base and tip of the papillary collecting duct was not different between KD and CON rats (26.9 k 5.6% in KD vs 21.4 k 3.3% in CON at the base, P > 0.05;and 12.4 f 1.5% in KD vs 10.4 k 1.4% in CON at the tip, P > 0.05). Furthermore, reabsorption of water or urea between the base and tip of the papillary collecting duct was not decreased in KD as compared to CON rats (water reabsorption was 57.8 f 4.4% in KD and 55.9 k 5.1 1% in CON and urea reabsorption was 45.0 k 6.5% in KD and 45.9 k 5.4% in CON, P > 0.05). These results demonstrate that water reabsorption, but not urea reabsorption, is impaired in renal tubules proximal to the accessible papillary collecting duct in hydropenic rats. o 1985