Additional effects of combination therapy of antihypertensive medication on aortic elastic properties beyond blood pressure lowering effect in spontaneously hypertensive rats

Abstract

Abstract Background Combination therapy in the treatment of hypertension provides better therapeutic efficacy, improved tolerability by lowering the dose and reduced potential for side effects than monotherapy. Especially, combinations of calcium channel blocker (CCB), angiotensin receptor blocker (ARB) or diuretics (thiazide) are generally effective and well tolerated regimen in antihypertensive treatment. However, we have focused more on the antihypertensive power of the combination therapy rather than the effect on the vessel itself. Purpose The purpose of this study is to determine the efficacy of antihypertensive medications as ARB and CCB and its combination with or without thiazide on the aortic structural and functional properties beyond the effect of blood pressure (BP) lowering. Methods Fourteen-week-old male spontaneous hypertensive rats were randomly divided into 5 groups, and treated with 1) vehicle (V), 2) amlodipine besylate (A), 3) olmesartan (O), 4) combined amlodipine and olmesartan (AO) or 5) combined amlodipine, olmesartan and thiazide (AOD), respectively. After 8 weeks of treatment, hemodynamic parameters and structural and functional properties of aorta as intima-media thickness (IMT) and velocity vector imaging (VVI) parameters of aorta including fractional area change (FAC), circumferential strain (CS) and strain rate (CSR) were assessed in each group and collagen contents of aorta were quantified as well. Results During the study period, systolic and diastolic BP were serially decreased in all treatment groups. Especially, AOD group showed lowest systolic and diastolic BP levels and also showed smallest IMT and vessel area and highest elasticity (FAC and CS) among the other groups (p<0.01) at 8 weeks (Table 1). In histologic analysis, collagen contents of aorta in all treatment groups showed significant associations with BP, IMT and VVI parameters (FAC, CS, CSR) (p<0.05), respectively. Particularly, aorta of AO and AOD groups showed significantly lower levels of collagen contents than that of control group. (p< 0.05) (Figure 1) Conclusion(s) Beyond the BP lowering effect, combination of amlodipine and olmesartan with or without thiazide minimize structural changes and shows better protection for the progression of arteriosclerosis than individual monotherapy in treatment of hypertension.Table 1Figure 1