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-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.
Santos
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RA
Laboratório de Hipertensao, Departmento de Fisiologia e Biofísica, Belo Horizonte, Brazil.
Simões e Silva
A C
AC
Magaldi
A J
AJ
Khosla
M C
MC
Cesar
K R
KR
Passaglio
K T
KT
Baracho
N C
NC
D000803:Angiotensin I; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D008297:Male; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000502:physiology; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology*
C092006:7-Ala-angiotensin (1-7); D010446:Peptide Fragments; D000804:Angiotensin II; D000803:Angiotensin I; C118790:angiotensin I (1-7)