Evidence for a physiological role of angiotensin-(1-7) in the control of hydroelectrolyte balance

In this study we evaluated the possibility that angiotensin-(1-7) [Ang-(1-7)] acts as an endogenous osmoregulatory peptide by determining the effect of acute administration of its selective antagonist [D-Ala(7)]Ang-(1-7) (A-779) on renal function parameters in rats. In addition, we investigated the physiological mechanisms involved in the antidiuretic effect of Ang-(1-7). The antidiuretic effect of Ang-(1-7) (40 pmol/0.05 mt per 100 g BW) in water-loaded rats was completely blocked by A-779 (vehicle-treated, 3.34+/-0.43 mL/h; Ang-(1-7), 1.48+/- 0.23; A-779, 2.72+/-0.35; Ano-(1-7) plus A-779, 3.26+/-0.49). In contrast, the antidiuretic effect of Ang-(1-7) was not significantly changed by a vasopressin V-2 receptor antagonist in a dose that completely blocked the antidiuresis produced by an equipotent dose of vasopressin. In addition, Ang-(1-7) administration did not significantly change vasopressin plasma levels in water-loaded rats. The antidiuretic effect of Ang-(1-7) in water-loaded rats was associated with a reduction of creatinine clearance (0.68+/-0.04 versus 1.38+/-0.32 mL/min in vehicle-treated rats, P<.05) and an increase in urine osmolality (266.8+/-32.7 versus 182.5+/-14 mOsm/kg in vehicle-treated rats, P<.05). An effect of Ang-(1-7) in tubular water transport was demonstrated in vitro by a fourfold increase in the hydraulic conductivity of inner medullary collecting ducts in the presence of 1 nmol/L Ang-(1-7). Subcutaneous administration of A-779 (2.3 to 9.2 nmol/100 g) produced a significant increase in urine volume (4.6 nmol/100 g, 0.45+/-0.12 mL/h; vehicle-treated rats, 0.16+/-0.03 ml/h; P<.05) comparable to that of acute administration of a vasopressin V-2 receptor antagonist. The diuretic effect of A-779 was associated with an increase in creatinine clearance and decrease in urine osmolality. In contrast, no significant effects on urine volume were observed after systemic administration of angiotensin subtype 1 or 2 receptor antagonists (DuP 753 and CGP 42112A, respectively). These findings suggest that endogenous Ang-(1-7), acting on specific receptors, participates in the control of hydroelectrolyte balance by influencing especially water excretion.