Effect of a Dihydropyridine-Type Calcium Channel Blocker on Vascular Remodelling after Experimental Balloon Angioplasty

Alexander      F. Kranzhofer; Oliver      Weingartner; Martin      Oberhoff; Karl      R. Karsch

Abstract

Objective: Aim of the study was to evaluate the influence of the dihydropyridine derivative BW 9798 on intimal hyperplasia in a carotid artery injury model of New Zealand White rabbits on a high cholesterol diet. Methods: In carotid arteries of 50 New Zealand White rabbits atherosclerotic lesions were induced by cholesterol diet and electrostimulation of the artery. In 40 animals the resulting primary lesion was subjected to balloon angioplasty (BA). Three days prior BA animals received BW 9798 or placebo per os until sacrifice three days or 28 days after BA. Results: BW 9798 led to increased cross sectional area by 128.3% and an increased luminal area by 157% after 28 days after BA compared with placebo. However the degree of stenosis did not significantly decrease. The cell count of the different layers of the arteries decreased by 64.5% in the intima and by 62.6% compared with placebo treated animals after BA. Additionally the number of smooth muscle cell (SMC) layers in the neointima was significantly lower in BW 9798 treated animals than in placebo animals (8±3 vs 14±9, p < 0.05) although the proliferation was not changed by BW 9798 treatment 3 days after BA. Conclusion: BW 9798 leads to significant changes in vessel wall geometry although the influence on vascular remodelling of this compound is unclear. It can be speculated that the compound affects the homeostasis of extracellular matrix, invasion of inflammatory cells into the vessel wall and the expression of cytokines. However, further investigation needs to clarify the role of BW 9798 on remodelling after BA.

Keywords: Calcium antagonist, rabbit, remodelling, restenosis, Dihydropyridine-Type Calcium Channel, Balloon Angioplasty, intimal hyperplasia, carotid artery injury, cholesterol, atherosclerotic lesions, BW 9798, smooth muscle cell, homeostasis, cytokines, percutaneous transluminal coronary angioplasty, coagulatory system, PDGF antagonist trapidil, anaesthesia, polypropylene suture, bromodeoxyuridine, deoxycytidine, Perfusion Fixation, paraformaldehyde, paraffin, hematoxylin, eosin, biotin-avidin method, Monocytes, stenosis, Macrophage, Cell Density, dihydropyridine, calcium antagonists, phosphorylation, calcium channel blockers, intima hyperplasia, L-type channels, vasodilatation, amlodipine, nifedipine, metalloproteinase, iNOS, verapamil