A B S T R A C T Vasopressin increased adenyl cyclase activity in homogenates of both inner and outer renal medulla of the rat. It also increased the concentration of cyclic 3',5'-adenosine monophosphate (AMP) in slices of both inner and outer medulla but not in renal cortex. In the inner medulla, a concentration of prostaglandin E1 (PGE1), which was ineffective by itself significantly reduced the stimulation of adenyl cyclase activity and cyclic AMP concentration induced by vasopressin. These results are consistent with the hypothesis that PGE1 can compete with vasopressin for adenyl cyclase-binding sites. However, the findings in the outer medulla suggest the situation is more complex. Although 10 M PGE1 had no effect by itself and inhibited the vasopressin-induced elevation of cyclic AMP, larger amounts of PGE1 increased both adenyl cyclase activity and cyclic AMP levels. The maximum effect on the latter parameter was at least 6 times as great as that of maximum amounts of vasopressin.

A B S T R A C T Catecholamines have several physiological effects on the kidney. These include: (a) stimulation of renin synthesis in the cortex; (b) antidiuresis by beta adrenergic agents; and (c) diuresis by alpha adrenergic stimulation. The role of cyclic 3',5'-adenosine monophosphate (cyclic AMP) in the renal actions of catecholamines was evaluated by measuring the effects of several adrenergic agents on cyclic AMP concentration in the dog kidney.Beta adrenergic activity increased cyclic AMP concentration in the renal cortex, a finding consistent with the hypothesis that beta-adrenergic stimulation augments renin synthesis by increasing cyclic AMP generation.Beta adrenergic stimulation, like vasopressin, increased cyclic AMP concentration in the renal medulla. This suggests that beta adrenergic stimulation causes antidiuresis by augmenting cyclic AMP generation in the renal medulla.Alpha adrenergic activity inhibited the effect of vasopressin to stimulate cyclic AMP generation. These results support the hypothesis that the diuretic effect of alpha adrenergic stimulation is mediated by inhibition of the effect of vasopressin to increase cyclic AMP generation.

The effect of aging on urinary concentrating ability and the pathogenic mechanism involved were investigated in Fischer 344 rats. While the rats had free access to drinking water, 24-mo-old rats were polydipsic and polyuric compared with 6- and 12-mo-old rats. The maximum urinary concentrating ability after 40-58 h of water deprivation was not different between 6- and 12-mo-old rats (Uosmol 2,941 +/- 173 vs. 2,706 +/- 96 (SE) mosmol/kg), but it was significantly decreased in 24-mo-old rats (1,885 +/- 172 mosmol/kg, P less than 0.01). Similarly, although 5 mU/ml vasopressin increased the concentration of cAMP and papillary slices in 12-mo-old rats (delta +2.81 +/- 0.62 pmol/mg tissue, P less than 0.01), the same concentration of vasopressin failed to increase the cAMP concentration in 24-mo-old rats (delta +0.25 +/- 0.21 pmol/mg tissue, P greater than 0.05). In the adenylate cyclase preparation of renal papilla, the response to low concentrations of vasopressin was diminished in 24-mo-old rats. The dose-response curve was shifted to the right and the ED50 concentration of vasopressin was increased in 24-mo-old rats compared with 12-mo-old rats: 1.40 +/- 0.12 mU/ml vasopressin vs. 3.04 +/- 0.22. These results suggest that the decrease in vasopressin-dependent cAMP generation may in part be responsible for the impairment of urinary concentrating ability in 24-mo-old rats.

A B S T R A C T The effects of calcium on the renal actions of parathyroid hormone (PTH) were studied in vivo and in vitro. In parathyroidectomized rats, variable levels of blood calcium concentration were induced by intravenous infusion of calcium. The renal responses to the injected PTH, i.e. phosphate and cyclic AMP excretion, were compared in these animals. After PTH injection, the increases of both phosphate and cyclic AMP excretion were less in the calcium-infused animals than in the control group without calcium infusion. There was an inverse correlation between the renal responses to PTH and plasma calcium concentration of 4.2-13.5 mg/100 ml. But calcium had no effect on phosphate excretion induced by infusion of dibutyryl cyclic AMP. In the in vitro experiments, the increase of cyclic AMP concentration in response to PTH was less in renal cortical slices taken from the calcium-infused animals than in ones from the control group without calcium infusion. Calcium also inhibited the activation of renal cortical adenylate cyclase in response to PTH, but calcium had no effect on phosphodiesterase. The data indicate that calcium directly inhibits renal actions of PTH both in vivo and in vitro. Such inhibitory mechanism is probably at or before the step of PTHdependent cyclic AMP generation in the kidney. INTRODUCTIONParathyroid hormone (PTH) 1 plays a major role in the regulation of the concentrations of calcium and phosphate in plasma. This appears to be accomplished primarily by a reciprocal relationship between the concentration of ionized calcium in plasma and the rate of

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.