Benefits and demerits of antihypertensive therapy by high-dose calcium channel blocker in severely hypertensive rats.
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 228 mmHg in the control group, 201 in the low dose 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Ogawa
Y
Y
Department of Medicine, Dokkyo University School of Medicine, Mibu, Japan.
Ishimitsu
T
T
Tsukada
H
H
Yagi
S
S
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D001835:Body Weight / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000627:therapeutic use; D006332:Cardiomegaly / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D015737:Nisoldipine / Q000008:administration & dosage* / Q000627:therapeutic use; D051381:Rats; D011918:Rats, Inbred SHR; D013997:Time Factors
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D015737:Nisoldipine