Effects Of Combination Of Amlodipine And Atrovastatin On Aortic Elasticity And Remodeling In Spontaneously Hypertensive Rats

Objective To investigate the effects of combined administration of amlodipine and atrovastatin on aortic elasticity and remodeling in spontaneously hypertensive rats. Methods 40 male spontaneous hypertensive rats (SHR) were randomly allocated into vehicle group (n=10), amlodipine-treated group [n=10, amlodipine 10 mg/(kg·d)], atorvastatin-treated group [n=10, atorvastatin 10 mg/(kg·d)], and combination group [n=10, atorvastatin 10 mg/(kg·d) and amlodipine 10 mg/(kg·d)]. Another 10 normotensive wistar-kyoto (WKY) rats were served as control group. Both the vehicle group and WKY group were intragastrically administrated with the same amount of distilled water for 12 weeks. Arterial pulse wave velocity (PWV), aortic augmentation index (AI), aortic medium thickness (MT), luminal radius (LR), and the ratio of MT/LR were measured 12 weeks after treatment. The content of collagen of aortic segment was evaluated by Masson trichrome staining. The content of hydroxyproline was measured by alkaline hydrolysis. The apoptosis rate of vessel smooth muscular cells in every group was analyzed by TUNEL method. Result After 12 weeks treatment, PWV and AI, aortic MT, MT/LR, and contents of aortic collagen in each SHR groups was significantly higher than those in WKY group (P<0.05). There were no significant differences among the level of lipid in each SHR groups. Although the blood pressure of the amlodipine-treated group and combination group decreased, it showed no significant difference between them. As compared with the vehicle group, aortic AI, aortic MT, MT/LR and contents of collagen in amlodipine-treated group, atorvastatin-treated group and combination group significantly decreased, but the apoptosis rate of smooth muscular cells increased. In amlodipine-treated group and combination group, PWV significantly decreased compared with the vehicle group. Compared with the amlodipine-treated group, the aortic AI, MT, MT/LR, and contents of collagen in the combination group significantly decreased, the apoptosis rate of smooth muscular cells increased. Conclusion Compared with amlodipine, combined application of amlodipine and atrovastatin improves the elastic properties of the aorta. The underlying mechanism may be associated with the decrease of aortic collagen content and improvement of aortic remodeling. These beneficial effects seem to be independent of lipid lowering effect of atorvastatin.