Platelet and endothelial function : Polycystic Ovary Syndrome and the renin-angiotensin system.

The phenomenon of platelet hyperaggregability and decreased platelet responsiveness to nitric oxide (also termed as nitric oxide resistance), documented in several cardiovascular disease states, is associated with adverse cardiovascular outcomes. The series of experiments described in this thesis address primarily some aspects of the pathophysiology, epidemiology and therapy of the phenomenon of end-organ resistance to nitric oxide (NO) in two important conditions, that are closely associated with cardiovascular risk factors and disease states:- Polycystic ovary syndrome, which is closely linked with the metabolic syndrome and premature subclinical atherosclerosis. The renin-angiotensin system, which is recognized as a significant mediator in the pathophysiology of a number of cardiovascular disease states. The first study examined the epidemiology/pathophysiology of putative platelet/endothelial dysfunction in young individuals with PCOS. The subsequent studies focused on the potential impact of the renin-angiotensin system on platelet and endothelial function. This mechanistic review is set in the context of a number of recent major clinical studies which have demonstrated surprising efficacy of certain angiotensin-converting enzyme (ACE) inhibitors (ramipril and perindopril) in the prevention of thrombotic processes. Thus we tested the hypothesis whether ACE inhibitor ramipril sensitizes platelets to NO (as a potential mechanism for improved cardiovascular outcomes) in a high risk patient cohort. In addition, particular attention will be given to the emerging role of the heptapeptide Angiotensin- (1-7), a possible physiological antagonist to Angiotensin II in the vasculature and the limitation of the current literature concerning potential effects of the renin-angiotensin system on thrombotic mechanisms.Thesis (Ph.D.) - University of Adelaide, School of Medicine, 200