| Injured arteries have different characteristics than normal uninjured arteries with regards to tissue expression of the renin-angiotensin system. Indeed, angiotensin-converting enzyme (ACE) and angiotensin (Ang) II AT 1 receptor expressions are upregulated in damaged vascular tissue. Nevertheless, the functional and structural consequences of these upregulations remain unclear. The aim of this thesis was to better characterise the role of the AngII pathway in vascular reactivity and remodeling after balloon angioplasty in the rat carotid artery and aorta. The contractile responses to AngI or AngII in the presence of ACE inhibitors or AT1 antagonists were evaluated. Our results demonstrate that ACE is not the rate limiting step for the contractile responses of AngI in injured arteries. However, ACE overexpression in injured arteries renders this tissue resistant to ACE inhibitors. Subsequently, the role of vascular smooth muscle cell apoptosis induced by anti-hypertensive agents was determined in the context of the prevention and the regression of neointimal lesions caused by angioplasty. Our studies show that AT 1 receptor blockade prevents the development of a neointima and causes the regression of a pre-existing neointima by inducing vascular smooth muscle cell apoptosis. Apoptosis was observed almost selectively in neointimal cells comparatively to medial cells. Similar results were also observed with another anti-hypertensive agent, the dihydropyridine calcium channel blocker nifedipine. Possible mechanisms controling the induction of apoptosis are discussed in this thesis. The potential of certain therapeutic agents used in the clinical setting to prevent and regress vascular lesions by a mechanism involving apoptosis could represent a novel therapeutic tool for the treatment of human vascular occlusive diseases. |
