Failure of an angiotensin II antagonist to influence isoprenaline-induced antidiuresis in rats.

The purpose of this study was to elucidate the role of angiotensin II in isoprenaline-induced antidiuresis by use of the competitive angiotensin II antagonist saralasin. Isoprenaline is known to enhance the formation of angiotensin II. Since angiotensin II has been shown to increase proximal tubular salt and volume reabsorption and to decrease renal fluid and salt excretion the renal effects of isoprenaline might, at least partly, be mediated by angiotensin II. Isoprenaline, infused at 0.1 microgram/kg . min i.v. into anaesthetized rats, led to a marked decrease of urine flow, sodium and potassium excretion and to an increase in urinary osmolality, confirming previous data. Effective renal plasma flow increased significantly. Immediately after onset of the isoprenaline infusion a transient small fall in GFR was observed. On continuation of the infusion, GFR recovered, but marked antidiuresis persisted. Changes in renal hemodynamics, therefore, can be excluded as being responsible for the antidiuretic effect. Saralasin, infused at 6 micrograms/kg . min i.v., did not affect isoprenaline-induced antidiuresis, antinatriuresis, antikaliuresis, and the increase in urinary osmolality, but prevented the rise in renal plasma flow observed during isoprenaline infusion, probably as a consequence of a weak angiotensin II-like effect of saralasin on renal vessels. It is concluded that angiotensin II does not play a role in isoprenaline-induced antidiuresis. The results are compatible with the view that beta-adrenoceptor stimulation may directly affect the tubular handling of water and salt.