The effect of dopamine receptor blockade on natriuresis is dependent on the degree of hypervolemia.

A number of different physiological factors and systems have been suggested to be responsible for the natriuretic effect following acute isotonic volume expansion (VE). The variation in suggestions may depend on the prevailing status of the systems governing fluid and electrolyte balance before VE, on the expansion medium and on the rate and degree of VE. A study was performed to determine whether the previously documented attenuating effect of dopamine receptor blockade on natriuresis induced by VE is dependent on the degree of hypervolemia. Anesthetized rats were pretreated with the dopamine receptor blockers haloperidol (1 mg.kg-1 body weight, i.p.), SCH 23390 (30 micrograms.hr-1.kg-1 i.v.) or vehicle and then subjected to VE at 2, 5 or 10% of body weight per hour. VE at 2, 5 and 10% increased sodium excretion in vehicle-pretreated animals 6-, 29- and 130-fold, respectively. In the haloperidol-pretreated animals the natriuretic response (accumulated sodium excretion) to VE was attenuated by 67% (P less than 0.05), 46% (P less than 0.05) and 22% (NS) at the three degrees of expansion, respectively. The corresponding attenuation in SCH 23390-treated animals were 60% (P less than 0.05), 56% (P less than 0.05) and 19% (NS), respectively. The gradual decrease in attenuation indicates that at varying degrees of hypervolemia, different physiological systems contribute differently to the renal natriuretic response. The dopamine system seems to be relatively more important in promoting natriuresis at the lower (physiological) range of hypervolemia whereas in the high range other factors have a greater impact.