This study was conducted to determine potentially differential effects between an
angiotensin II type 1 (AT(1)) receptor antagonist and an
ACE inhibitor on systemic, renal, and glomerular hemodynamics and pathological changes in spontaneously hypertensive rats (SHR) with
N(omega)-nitro-L>-arginine methyl ester (
L-NAME)-exacerbated
nephrosclerosis. The hemodynamic, renal
micropuncture, and pathological studies were performed in 9 groups of 17-week-old male SHR treated as follows: group 1, controls (n=16); group 2,
candesartan (10 mg/kg per day for 3 weeks) (n=7); group 3,
enalapril (30 mg/kg per day for 3 weeks) (n=8); group 4,
candesartan (5 mg/kg per day) plus
enalapril (15 mg/kg per day for 3 weeks) (n=9); group 5,
L-NAME (50 mg/L in
drinking water for 3 weeks) (n=17); group 6,
L-NAME (50 mg/L) plus
candesartan (10 mg/kg per day for 3 weeks) (n=7); group 7,
L-NAME (50 mg/L) for 3 weeks followed by
candesartan (10 mg/kg per day) for another 3 weeks (n=8); group 8,
L-NAME (50 mg/L) plus
enalapril (30 mg/kg per day for 3 weeks) (n=7); and group 9,
L-NAME (50 mg/L) plus
enalapril (30 mg/kg per day) and the
bradykinin antagonist icatibant (500 microg/kg SC per day via osmotic minipump for 3 weeks) (n=7). Both
candesartan and
enalapril similarly reduced mean arterial pressure and total peripheral resistance index. These changes were associated with significant decreases in afferent and efferent glomerular arteriolar resistances as well as glomerular capillary pressure. Histopathologically, the glomerular and arterial injury scores were decreased significantly, and left ventricular and aortic masses also were diminished significantly in all treated groups.
L-NAME-induced urinary
protein excretion was prevented by both
candesartan and
enalapril. Thus, both AT(1) receptor and ACE inhibition prevented and reversed the pathophysiological alterations of
L-NAME-exacerbated
nephrosclerosis in SHR. Itatibant only blunted the
antihypertensive effects of
enalapril but did not attenuate the beneficial effects of ACE inhibition on the
L-NAME-induced
nephrosclerosis. Thus, the AT(1) receptor antagonism and ACE inhibition have similar renal preventive effects, which most likely were achieved through reduction in the effects of
angiotensin II, and ACE inhibition of
bradykinin degradation demonstrated little evidence of renoprotection.