Effects of a newly developed Ca2+ channel antagonist, (4R)-(-)-2-(nicotinoylamino)ethyl 3 nitrooxypropyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl) 3,5-pyridine-dicarboxylate (CD-832), on hypertensive complications in
stroke-prone spontaneously hypertensive rats (SHRSPs) were compared with effects of
diltiazem. We examined changes in histological and hematological parameters in SHRSPs given the following treatments at 8 to 20 weeks of age: (a)
CD-832; (b)
diltiazem; (c) no treatment.
CD-832 and
diltiazem were added to the diet, in doses of 0.05 and 0.15% (approximately 30 and 100 mg/kg per day), respectively, throughout the experimental period. In untreated control SHRSPs, systolic blood pressure increased and severe renal lesions such as fibrinoid
necrosis, smooth muscle proliferation, glomerular and tubular lesions and some cardiac
fibrosis were observed at age 20 weeks. 12-week repeated-administration of
CD-832 and
diltiazem led to a comparable
hypotension and decreased heart rate.
CD-832 and
diltiazem decreased the ratios of weights of kidney and heart to
body weight and the concentration of blood
urea nitrogen and
creatinine in serum, compared to values in controls. In SHRSPs treated with
CD-832 and
diltiazem, the incidence of renal lesions and myocardial
fibrosis was significantly reduced when compared with control SHRSPs. These results suggest that 12-week repeated-administration of
CD-832 prevents the development of
hypertension and the incidence of organ damage in SHRSPs.
CD-832 and
diltiazem were equally efficacious in preventing organ damage but this organ-protective effect was obtained at a lower dose for
CD-832 (30 mg/kg per day) than that of
diltiazem (100 mg/kg per day).