This study examined the protective effects of a calcium channel blocker, nisoldipine (NSL), against organ damage secondary to severe hypertension. Severe hypertension was induced in male 7-week-old spontaneously hypertensive rats (n=21) by heminephrectomy and substitution of 1% NaCl solution for drinking water. They were fed a chow containing 0%, 0.03% (low dose) or 0.1% (high dose) NSL for 12 weeks. The systolic blood pressures after 12 weeks were 228mmHg in the control group, 201 in the low

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... se NSL group and 188 in the high dose NSL group. Body weight gain was blunted in the high dose NSL group (at 12 weeks: control 289g; low dose NSL 286; high dose NSL 263, p<0.04). Although a further reduction in cardiac weight was seen in the high dose NSL rate (low NSL -5.2%, p<0.05; high NSL -9%, p<0.01), reductions in aortic thickness did not differ between the 2 doses (low NSL -18%, p<0.001; high NSL -17%, p<0.001). Moreover, dose-dependent effects of NSL treatment were absent for such endpoints as plasma creatinine (low NSL -15%, p<0.04; high NSL -17%, p<0.05), glomerular filtration rate (low NSL +21 %, p<0.05; high NSL +20%, p<0.03) and urinary protein excretion (low NSL -22%, p<0.05; high NSL -29%, p<0.02). Thus, a high dose calcium channel blocker hampered growth and did not further improve vascular wall thickening or renal injury in severely hypertensive rats. Therefore, in treating hypertension, combination of other antihypertensive drugs may be recommended rather than using high doses of calcium channel blockers. (Jpn Heart J 35: 353-361, 1994)