Effects of amlodipine on bone metabolism in male albino Wistar rats

Iveta Gradošová,Klára Švejkovská,Pavel Živný,Helena Živná,Vladimír Palička,Aleš Tichý

doi:10.2754/avb201180040391

Abstract

Amlodipine (dihydropyridine-type calcium channel blocker) is a widely used agent for the treatment of hypertension in human and veterinary medicine but detailed information about its effects on bone metabolism are missing. Therefore, the aim of our study was to investigate the effect of amlodipine on bone metabolism in male albino Wistar rats. Amlodipine (0.3 mg/100 g body weight; gavage) was administered to 8 rats for 8 weeks. Control group (n = 8) received aqua pro inj. (0.2 ml/100 g body weight; gavage). Bone marker concentrations of carboxy-terminal cross-linking telopeptide of type I collagen (CTX-I) and aminoterminal propeptide of procollagen type I in serum, and of bone alkaline phosphatase (BALP) in both serum and bone homogenate were measured by enzyme immunoassay. We investigated the expression of bone morphogenetic protein 2 (BMP-2) in proximal tibia using Western blotting, and bone mineral density was measured by Dual-energy X-ray Absorptiometry in lumbar and caudal vertebrae and in femoral areas. Mechanical properties of the femurs were measured by three-point bending of the shaft and compression testing of the femoral neck. After 8 weeks of amlodipine administration there was a significant decrease in serum concentrations of BALP (p= 0.0009) and CTX-I (p= 0.003), and the content of BALP in bone homogenate (p= 0.026) compared to the control. In addition, Western blot analysis indicated increased BMP-2 protein concentration after amlodipine administration. Our findings suggest that amlodipine has a retarding influence on bone metabolism in rats by decreasing bone turnover, which probably in consequence increases expression of BMP-2.

Highlights

Cardiovascular diseases are one of the leading causes of death for people in developed countries world-wide
We investigated the expression of bone morphogenetic protein 2 (BMP-2) in proximal tibia using Western blotting, and bone mineral density was measured by Dual-energy X-ray Absorptiometry in lumbar and caudal vertebrae and in femoral areas
Our findings suggest that amlodipine has a retarding influence on bone metabolism in rats by decreasing bone turnover, which probably in consequence increases expression of BMP-2

Summary

Introduction

Cardiovascular diseases are one of the leading causes of death for people in developed countries world-wide. Hypertension and osteoporosis are frequent diseases among people of higher age. Both are induced by interaction of many genetic and environmental factors (Shimizu et al 2008). The first-choice antihypertensive drugs include the calcium channel blockers. Amlodipine is a derivate of dihydropyridine and is one of the 3rd generation calcium channel blockers. L-type calcium channels have been shown in a rat osteoblast-like cell line (Morain et al 1992). Many studies indicate that calcium channel blockers influence bone metabolism, but at present there is no agreed opinion about whether they are beneficial or not. Little information has been published on the effect of amlodipine on bone metabolism (Nishiya and Sugimoto 2001; Halici et al 2008; Ushijima et al 2010)

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