To determine whether there is a difference in the effects of T- and L-type
calcium antagonists on systemic, renal, and glomerular hemodynamics, the pathological changes of
N(G)-nitro-L-arginine methyl ester (
L-NAME)-exacerbated
nephrosclerosis and clinical alterations were investigated in spontaneously hypertensive rats (SHR). Seven groups of 17-week-old male SHRs were studied: Group 1, control; Group 2,
mibefradil, 50 mg. kg(-1). d(-1); Group 3,
L-NAME in
drinking water, 50 mg/L; Group 4,
L-NAME (50 mg/L) plus
mibefradil (50 mg. kg(-1). d(-1)); Group 5,
L-NAME (50 mg/L) plus
amlodipine (10 mg. kg(-1). d(-1)); Group 6 and 7,
L-NAME (50 mg/L) for 3 weeks followed by
mibefradil (50 mg. kg(-1). d(-1)) or
amlodipine (10 mg. kg(-1). d(-1)), respectively, for the subsequent 3 weeks. Both the T- and L-channel
calcium antagonists similarly reduced mean arterial pressure and total peripheral resistance index. These changes were associated with significant decreases in afferent and efferent glomerular arteriolar resistances and the ultrafiltration coefficient (P<0.01). Furthermore, the histopathological glomerular and arterial injury scores and urinary
protein excretion were also significantly improved (P<0.01), and left ventricular and aortic masses were significantly diminished in all treated groups. Both drugs,
mibefradil and
amlodipine, had effects of increasing the single-nephron glomerular filtration ratio (SNGFR), and single-nephron plasma flow (SNPF), and of reducing glomerular afferent arteriolar resistance and urinary
protein excretion. Thus, the T-type (
mibefradil) and L-type (
amlodipine)
calcium antagonists each prevented and reversed the pathophysiological alterations of
L-NAME-exacerbated hypertensive
nephrosclerosis in SHR. The T-type
calcium antagonist (
mibefradil) seemed to have been more effective than the L-type
amlodipine antagonist and it produced a greater reduction in afferent arteriolar resistance while preserving SNGFR.