AVP and aldosterone at physiological concentrations have synergistic effects on Na+ transport in rat CCD

These studies examined whether the previously reported synergism between pharmacological doses of deoxycorticosterone (DOC) and arginine vasopressin (AVP) also occur at physiological concentrations of aldosterone and AVP. We examined the dose-response of salt transport, as measured by the lumen-to-bath 22Na+ flux (J1 --> b) and transepithelial voltage (VT), and of osmotic water permeability (Pf), to AVP in isolated perfused cortical collecting ducts (CCDs) from three groups of rats: (1) implanted with a 1 mg d-aldosterone pellet, which produced a moderately elevated, but physiologically relevant, plasma aldosterone concentration of 18.4 +/- 2.6 ng/dl; (2) implanted with a 2.5 mg DOC pellet (a high pharmacological dose); and (3) untreated rats, Pf reached the same maximal value in all three groups, and the concentration of AVP producing one-half the maximal Pf response (K0.5) was not significantly different among the three groups, ranging from 5 to 10 pM. There was a significantly greater increase in J1 --> b and hyperpolarization of VT with increasing AVP in both groups of treated rats than in the untreated group. The maximum values of J1 --> b and VT achieved at high AVP concentrations were not significantly different in CCDs from the aldosterone-treated and DOC-treated groups, but they were significantly higher than in the CCDs from untreated rats. Although maximal VT values achieved with DOC and aldosterone treatment were the same, the AVP K0.5 for VT were significantly lower in the DOC-treated than in the aldosterone-treated group. Although not statistically significant, the same trend was observed for J1 --> b. We conclude that AVP and aldosterone synergistically stimulate Na+ reabsorption at physiological concentrations of both hormones; however, VT (and probably Na+ reabsorption, which is generally proportional to VT) reaches maximum values at lower AVP concentrations when pharmacological doses of DOC are employed.