Grant: Operating Grant

We showed that treatments with antioxidants or inhibitors of B1 receptor (B1R) for kinins (local hormone and brain mediator) reversed hypertension and diabetes abnormalities in rat models. The B1R is absent in healthy subjects and its occurrence is the signature of a pathology. We propose that the oxidative stress increases the occurrence of kinin B1R which in turn perpetuates the oxidative stress and its harmful effects on vasculature and other target organs. This project is using an integrative approach to determine the mechanism by which kinin B1R can be induced by the oxidative stress and how this receptor can perpetuate the oxidative stress and causing vascular inflammation which accelerates the development of cardiovascular diseases. Inhibitors of kinin B1R are believed to prevent not only the deleterious effect of these peptides on the vasculature but also to act as potent anti-hypertensive drugs by inhibiting brain neuronal activity. Therefore, the site and mechanism of action of these inhibitors in the brain will be further investigated. This project will be carried out in two rat models of hypertension associated or not with diabetes. Several parameters will be measured in the whole animal (blood pressure, heart rate,plasma levels of insulin and glucose, insulin resistance) and in post-mortem tissues: tissue levels of B1 receptor and of various markers of inflammation and oxidative stress. This work should increase our understanding of the role of kinin B1R in diabetes and hypertension. Inhibitors of this receptor may offer a new therapeutic avenue in the treatment of these diseases. However, to warranty their clinical use, further information regarding the way they operate in our body is mandatory.