Antiatherosclerotic effects of nicardipine and nifedipine in cholesterol-fed rabbits.

Abstract

Dutch-belted rabbits fed a 2% cholesterol diet for 8 weeks developed atherosclerotic lesions that covered 37.2% +/- 3.5% of the aortic luminal surface. In samples of aortic arch, accumulation of cholesterol and triglyceride was also observed. Oral administration of nicardipine or nifedipine at dosages of 40 mg/kg twice daily for 8 weeks reduced plaque area by 49.2% and 58.7%, respectively. Nicardipine and nifedipine reduced cholesterol accumulation in the aortic arch by 74.5% and 69%, respectively. Triglyceride accumulation was totally abolished. Neither drug significantly altered cholesterol concentration of plasma low density lipoprotein or high density lipoprotein, although nicardipine produced a 42% reduction in cholesterol concentration of the d less than 1.006 g/ml fraction. The above results suggest potential therapeutic utility of nicardipine in atherosclerosis.

Nifedipine Induces Peroxisome Proliferator-Activated Receptor-γ Activation in Macrophages and Suppresses the Progression of Atherosclerosis in Apolipoprotein E-Deficient Mice

“…6 Monocytes subsequently adhere to the endothelial cells, cross the endothelial layer to enter the subendothelial space, differentiate into macrophages, and eventually become foam cells. Macro- Nifedipine, an L-type CCB, reduced the atherosclerotic plaque area in cholesterol-fed rabbits 18,19 and suppressed the progression of atherosclerosis in hypertensive patients. 20 -24 However, the mechanism(s) of nifedipine-induced antiatherosclerotic activity are not fully understood.…”

“…Nifedipine, an L-type CCB, reduced the atherosclerotic plaque area in cholesterol-fed rabbits 18,19 and suppressed the progression of atherosclerosis in hypertensive patients. 20 -24 However, the mechanism(s) of nifedipine-induced antiatherosclerotic activity are not fully understood.…”

Irbesartan but Not Amlodipine Suppresses Diabetes-Associated Atherosclerosis

“…Experimental evidence suggests that calcium antagonists reduce the severity of atherosclerosis in the nondiabetic context, including in cholesterol-fed rabbits and in primates. [5][6][7] Both Ang II subtype 1 (AT 1 ) receptor antagonists and calcium channel blockers have been demonstrated to have antiatherosclerotic effects in apoE-null mice. 8 -10 The present study was performed to compare the effects of treatment with an AT 1 receptor antagonist with treatment with a calcium channel blocker on the formation of atherosclerosis in the diabetic apoE-null mouse.…”

Nifedipine increases energy expenditure by increasing PGC-1α expression in skeletal muscle

“…Oxygen consumption (VO 2 ), carbon dioxide production (VCO 2 ), the respiratory exchange ratio (RER) and activity levels were determined (Light time; 13:00-17:00, Dark time; 1:00-5:00, air flow rate 0.50 l min À1 ) as previously described. 18 For exercise experiments, mice were allowed to adapt to an air-tight treadmill chamber (Model MK-680AT/02 M, Muromachi Co., Ltd) for 30 min (air flow rate 0.90 l min À1 ) at which point VO 2 and VCO 2 were stable; measurements were then continued for another 30 min while mice were in a sedentary state. Mice then exercised on a treadmill at a speed of 10 m min À1 , and VO 2 , VCO 2 and RER were measured for 30 min as previously described.…”

“…Nifedipine, a widely used antihypertensive drug, is thought to act mainly by blocking dihydropyridine receptor/L-type Ca channels on vascular smooth muscle cells. Nifedipine treatment reduces atherosclerotic plaques in cholesterol-fed rabbits, 2,3 and suppresses development and progression of atherosclerosis in hypertensive patients. 4,5 Nifedipine has recently been reported to have pleiotropic effects on endothelial cells, 6,7 cardiac muscle cells, 8,9 mesangial cells [10][11][12] and neurons, 13,14 through mechanisms independent of blocking Ca channels.…”