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The central goal of this thesis was to understand the functional relevance of genetic polymorphisms in cardiovascular diseases. Endothelial nitric oxide synthase (eNOS, NOS3) is a critical regulator of cardiovascular function and is altered in a number of cardiovascular diseases. The mechanistic contributions of genetic polymorphisms in the NOS3 gene have not been completely understood. Another important goal was to understand the mechanistic aspects of sepsis related cardiac failure. Reactive nitrogen species have been implicated along with impaired mitochondrial function. The exact mechanisms, interplay of these mediators and their time course is not completely understood. Intact endothelial function is a major regulator of cardiovascular function. Alterations in the endothelial nitric oxide (NO) production via endothelial nitric oxide synthase (eNOS, NOS3) have been implicated in vascular dysfunction. Moreover many genetic polymorphisms have been studied for their association with diseases and it has been established that NOS3 genetic polymorphisms may be a predisposing risk factor. These clinical studies are valuable, but fail t