(Hypertension. 1996;27:875-884.)
© 1996 American Heart Association, Inc.
Articles |
Evidence for a Physiological Role of Angiotensin-(1-7) in the Control of Hydroelectrolyte Balance
From Laboratório de Hipertensão, Departamento de Fisiologia e Biofísica, ICB-UFMG, Belo Horizonte, Brazil (R.A.S.S., A.C.S.S., K.T.P., N.C.V.B.); Department of Neuroscience, Cleveland (Ohio) Clinic Foundation (M.C.K.); and Laboratório de Pesquisa Básica, Departamento de Nefrologia, FMUSP, São Paulo, SP, Brazil (A.J.M., K.R.C.).
Correspondence to Robson A.S. Santos, MD, Departamento de Fisiologia e Biofísica, Av Antônio Carlos, 6627-ICB-UFMG, 31270-901, Belo Horizonte, MG, Brazil.
Abstract 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-Ala7]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 mL 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; Ang-(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 V2 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 182.8±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 V2 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.
Key Words: renin-angiotensin system • vasopressin • osmoregulation • angiotensin antagonists
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