Biphasic Effects of Graded Doses of Pitressin

Abstract

Pitressin was administered subcutaneously at three dose levels (20 mu, 100 mu and 1000 mu) to rats made hypertensive with DCA. The excretion of Na, K and water was followed in each case during two consecutive collection periods of 4 hours each. These two periods were selected as corresponding to the pressor and depressor phases of Pitressin action, respectively. The selection of control and hypertensive animals was based on a preliminary blood pressure determination obtained by direct electromanometry from the femoral artery. At the low dose level of 20 mu a simple antidiuretic effect predominates and is apparent during the first collection period. At the intermediate dose level of 100 mu the simple antidiuresis is still evident during the first collection period. The second collection period is, however, marked by well defined Na retention with a lesser degree of water retention. The Na retention is not preceded by any antecedent Na loss. At the high dose level of 1000 mu the first period is distinguished as a phase of marked Na loss. In this phase the excretions of water and K are also increased but these appear to be only secondarily affected. The second period is again marked by well defined Na retention. These effects also occur in the normal animal given this dose of Pitressin. These experiments are taken to demonstrate that the biphasic effect of Pitressin on salt and water handling may be elicited in both the salt loaded and nonloaded rat. Attention is also drawn to the fact that there is a rough correlation between the effects of Pitressin on blood pressure and on salt and water metabolism.