Background:
Acute Kidney Injury (AKI), a common disease of the urinary system, can
be induced by high doses of gentamicin (GM). The Renin-Angiotensin System exerts a key role in
the progression of the AKI since elevated intrarenal levels of Ang II, and ACE activity is found in
this condition. However, it is unknown whether oral administration of Ang-(1-7), a heptapeptide
that evokes opposite effects of Ang II, may attenuate the renal injuries induced by gentamicin.
Objectives:
To evaluate the effects of Ang (1-7) on GM-induced renal dysfunction in rats.
Methods:
AKI was induced by subcutaneous administration of GM (80 mg/Kg) for 5 days. Simultaneously, Ang-(1-7) included in hydroxypropyl β-cyclodextrin (HPβCD) was administered by gavage [46 μg/kg HPβCD + 30 μg/kg Ang- (1-7)]. At the end of the treatment period (sixth day), the
rats were housed in metabolic cages for renal function evaluation. Thereafter, blood and kidney
samples were collected.
Results:
The Ang-(1-7) attenuated the increase of the plasmatic creatinine and proteinuria caused
by GM but did not change the glomerular filtration rate nor tubular necrosis. Ang-(1-7) attenuated
the increased urinary flow and the fractional excretion of H2O and potassium observed in GM rats
but intensified the elevated excretion of sodium in these animals. Morphological analysis showed
that Ang-(1-7) also reduced the tubular vacuolization in kidneys from GM rats.
Conclusion:
Ang-(1-7) promotes selective beneficial effects in renal injuries induced by GM.