Grant: Operating Grant

The risk of developing cardiovascular diseases is enhanced by diabetes and obesity. We have shown, that oxytocin (OT), traditionally believed to be a hormone implicated in the reproduction has wide pleiotropic properties among other protects the heart against hypertrophy and failure. The action of OT is linked to the natriuretic peptides (NPs) and nitric oxide (NO) both important protective factors for the cardiovascular system. We have found that this cardio-protective system is down-regulated in db/db mice, an animal model for diabetes and obesity. Therefore, we are proposing to test the hypothesis that the reduction of cardiac OT-NPs system is linked to the development of type 2 diabetes and obesity and cardiovascular consequences. The treatment with BNP or oxytocin could be beneficial in alleviating the symptoms of diabetes, obesity and cardiovascular complications. In this proposal at first, we would like to learn at what point of development of diabetes and obesity the changes in cardio-protective mechanism involving OT-NPs-NO occurs. Secondly we plan to treat the animals, db/db mice, genetic model of diabetes and obesity with OT and BNP, both having beneficial effect on metabolic and cardiovascular functions. Improved understanding of the action of these hormonal systems during the development of cardiovascular diseases in diabetic and obese model represents a novel departure, a physiological approach to the management of diabetes, obesity and consequently cardiovascular disorders. Our recent discovery of an entire functional OT/OTR system in the heart and vasculature and demonstration of the role of this system in the heart regeneration such as cardiomyogenic properties of OT provide a solid argument for its role in cardiovascular system. The results of this study will offer new insight into potential mechanism of myocardial dysfunction and early mortality in obesity and diabetes.