Manidipine inhibits the progression of hypertension and atherosclerosis in endothelium-injured and cholesterol-fed Goldblatt 2K1C rats.
In the present study, arteriosclerotic change of the aorta was induced in rats. The effects of manidipine hydrochloride on the resulting hypertension and arteriosclerotic change were studied. In endothelium-injured cholesterol-fed Goldblatt 2K1C rats, moderate elevation of blood pressure was noted at 3, 4, and 5 weeks. Laboratory studies performed at the end of 6 weeks also showed hypercholesterolemia, accompanied by a reduction of triglycerides and HDL cholesterol. Regular doses of manidipine (200 or 500 mg/kg) resulted in a dose dependent inhibition of the blood pressure elevation and a reduction of HDL cholesterol, but had no effect on cholesterol or triglyceride levels. Morphological studies in endothelium-injured rats afflicted with hypercholesterolemia and hypertension, showed medial thickening and intimal hyperplasia. Hyperplasia of the intima was a result of excessive proliferation of the smooth muscle cells. These cells showed an unusually large number of fat droplets and were considered indicative of atheromatous plaque formation. In rats treated with manidipine, hyperplasia of the media was completely suppressed while hyperplasia of the intima was reduced by a minimum of 50%. This study demonstrated that hypercholesterolemia and hypertension produced arteriosclerotic change in endothelium-injured rats, which was inhibited by manidipine. It is not known whether antiarteriosclerotic action was involved in the antihypertensive effect of manidipine.
Sasaki
S
S
Second Department of Medicine, Kyoto Prefectural University of Medicine, Japan.
Kuwabara
T
T
Takenaka
K
K
Takesako
T
T
Itoh
H
H
Nakata
T
T
Takeda
K
K
Nakagawa
M
M
D000818:Animals; D001011:Aorta / Q000033:anatomy & histology / Q000187:drug effects; D001161:Arteriosclerosis / Q000139:chemically induced / Q000188:drug therapy* / Q000209:etiology; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002784:Cholesterol / Q000008:administration & dosage* / Q000097:blood / Q000633:toxicity; D004095:Dihydropyridines / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006978:Hypertension, Renovascular / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D009578:Nitrobenzenes; D010879:Piperazines; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009578:Nitrobenzenes; D010879:Piperazines; C054218:manidipine; D002784:Cholesterol