Effects of various antihypertensive drugs on the function of osteoblast

Several studies have suggested that high blood pressure is associated with the risk of bone loss. Since various antihypertensive drugs are in wide use for the treatment of hypertension, it is important to investigate the infl uences of these drugs on bone metabolism, Osteoblasts play a pivotal role i n the regulation of bone formation. During differentiation, they sequential ly express type I collagen, alkaline phosphatase (AI,P), other bone matrix proteins, and finally undergo mineral deposition. In this study, we examine d the effects of various antihypertensive drugs on the function of osteobla st using clonal MC3T3-E1 cells, Drugs examined include dihydropyridine-type calcium channel blockers (benidipine, amlodipine, and nifedipine), angiote nsin-converting enzyme (ACE) inhibitors (captopril, lisinopril, and enalapr il), and angiotensin II receptor type1 (AT1) antagonists (TCV-116 and KW-34 33), None of the ACE inhibitors or AT1 antagonists affected ALP activity or cellular DNA content significantly, In contrast, benidipine, amlodipine, a nd nifedipine increased ALP activity when used in amounts 1 pm, 100 nM, and 100 nM, respectively. Benidipine blocked calcium influx through the L-type voltage dependent calcium channel of MC3T3-E1 more potently than amlodipin e or nifedipine. These calcium channel blockers did not change collagen acc umulation. Benidipine significantly increased in vitro mineralization at a concentration of I nhl and higher, while amlodipine did so at 1 mum and nif edipine did not. Comparison of the effective concentration of each calcium channel blocker in our study with the reported maximum serum concentration of each drug suggests that benidipine, but not amlodipine or nifedipine, pr omotes mineral deposition in human.