The present study evaluates the participation of oxidative stress, tissue
angiotensin II (Ang II) and
endothelin (ET) in the effects of
losartan on blood pressure (BP), ventricular
hypertrophy and renal injury in spontaneously hypertensive rats (SHRs), and explores how these effects are modified when spontaneous
hypertension is transformed in a low-
renin model by the administration of
deoxycorticosterone acetate (
DOCA). The following groups were used: SHR-control, SHR+DOCA, SHR+losartan and SHR+
DOCA+
losartan. Tail systolic BP was measured once a week. After 9 weeks of treatment, direct BP and metabolic, morphological, biochemical and renal variables were measured.
DOCA administration to SHRs produced an increase in BP, ventricular
hypertrophy, renal weight,
proteinuria, renal histopathological lesions, urinary excretion of
isoprostane F2alpha and ET levels in the renal cortex.
Losartan reduced BP, plasma
malondialdehyde levels, urinary excretion of
isoprostane F2alpha, renal Ang II and renal and urinary levels of ET in the SHR and
DOCA-treated SHR groups.
Losartan increased plasma
nitrite/
nitrate in SHRs, but not in low-
renin DOCA-treated SHRs.
Losartan reduced ventricular
hypertrophy and ventricular Ang II in SHRs, but not in
DOCA-treated SHRs.
Losartan significantly decreased
proteinuria and renal injury in
DOCA-treated SHRs. We conclude that (i) the
DOCA-induced aggravation of
hypertension, ventricular
hypertrophy and renal injury in SHRs is accompanied by augmented oxidative stress and increased levels of ET in the renal cortex, which could contribute to their development; and (ii)
losartan reduced oxidative stress and renal Ang II and ET in SHRs and
DOCA-treated SHRs, which might contribute to its
antihypertensive and renoprotective effects, regardless of
renin status.