Background: Arteriosclerosis, characterized by remodeling and stiffening of large elastic arteries is the most significant manifestation of vascular aging. To determine whether new angiotensin receptor blocker (ARB), fimasartan prevent blood pressure elevation and arteriosclerosis in a rat model of medial elastocalcinosis obtained by the chronic administration of warfarin and vitamin K1 (WVK), we compared the effects of treatment with fimasartan, an ARB, on blood pressure and organ damage with amlodipine, a calcium channel blocker, atenolol, a beta-blocker and hydrochlorothiazide, a thiazide diuretic.
Methods and Results: Control Wistar rats were compared with rats receiving warfarin and vitamin K1 (WVK) for 5 weeks. The WVK rats were administered fimasartan 10mg/kg/day (low does), fimasartan 20mg/kg/day (high does), amlodipine 5mg/kg/day, atenolol 10mg/kg/day and thiazide 12.5mg/kg/day for 5 weeks. Baseline blood pressure were similar in all group. After 5 weeks, central systolic blood pressure (SBP) and peripheral SBP was increased in WVK rats (132±3.1 and 144±6.0 mmHg) compared with control rats(102±5.9 and 114±3.5 mmHg). However, central and peripheral systolic BP significantly reduced only by low does fimasartan (85±6.2 and 97±5.4 mmHg) and high does fimasartan(86±5.7 and 93±4.9 mmHg) (all p<0.01), but not by amlodipine (124+/-6.1 and 125±5.6 mmHg), atenolol (117±5.6 and 129±5.9 mmHg), and thiazide(119±2.7 and 125±4.8 mmHg). Similarly cardiac hypertrophy were reduced only by fimasartan treatment.
Conclusion: New ARB, fimasartan, significantly decreased central and peripheral systolic BP and cardiac hypertrophy in rat model of severe fibrosis and calcification in artery and isolated systolic hypertension. Therefore fimasartan may provide a novel and effective therapeutic agent in arteriosclerosis and vascular aging.
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