Inhibition Of Doxazosin On Proliferation Of Rat Vascular Smooth Muscle Cells

Objective : Restenosis which occurs after Percutaneous Transluminal Coronary Angioplasty ( PTCA ) is the major problem unsolved in coronary interventional therapy. In order to approach an effective methord to prevent restenosis, we observed the effect of Doxazosin ( Dox ) on the proliferation of rat aortic vascular smooth muscle cell ( VSMC ) and the interaction between Dox and nitric oxide ( NO ) in vitro. In the rat carotid artery injury model, we examined the effects of Dox on neointimal hyperplasia and NO production . Methods: 1. In the first part of the studies, Sprague-Dawley ( SD ) rats' thoracic aorta VSMCs were cultivated in vitro. The effects of Dox,NO and interleukin-1β( IL-1β) on VSMCs were determined by 3H-Thymidine ( 3H-TdR ) incorporation, synergistic effect between Dox and NO was examined. The release of NO stimulated by IL-1β was detected by nitrate reductase method. 2. In the second part of the studies, we established experimental models induced by external crushing. 56 SD rats were divided into four groups randomly: the control group,Dox group,NG-monomethyl-L-arginine ( L-NMMA ) group and Dox+L-NMMA group. Each group was treated with NS,Dox ,L-NMMA and Dox+L-NMMA respectively. 3 weeks later, followed by pathologic examination and morphometric analysis, the neointimal area (μm2),neointimal thickness (μm),percent area stenosis and I/M were analyzed using a computerized imagining system. NO production of injury vascular was determined by nitrate reductase method. Restults :1. In vitro: (1) Dox,NO and IL-1βhad antiproliferative effects on VSMC in dose-dependent manners; (2) Dox and NO synergistically inhibited the proliferation of VSMC; (3) There was obvious correlation between antiproliferative effect and NO production stimulated by IL-1β. 2. In vivo, administration of Dox was associated with a decrease in neointimal hyperplasia and an increase in NO production.Moreover, administration of the nitric oxide synthase ( NOS ) inhibitor L-NMMA was associated with a decrease in NO production and an increase in neointimal hyperplasia . Conclusion: These results indicate that Dox inhibits neointimal hyperplasia in the rat carotid artery injury model by inhibitting the proliferation of VSMC and increasing NO production of injury vascular, suggesting it be useful in preventing restenosis after PTCA...