Grant: Project Grant

Hypertension is the leading cause of death and disability in industrialized countries, accounting for 9.4 million deaths each year. In 2010, the estimated cost of hypertension treatment across Canada was ~ $13.9 billion, and the number is projected to rise to over $20 billion by 2020. While numerous effective antihypertensive drugs are available, up to 30% of patients are resistant to these treatments and do not respond to any available medication nor their combinations. In Canada, over 6 million are hypertensive, and in ~30% of these individuals, hypertension remains uncontrolled. Thus, additional therapeutics are needed to target this population of hypertensive individuals. Excessive dietary salt is strongly correlated with cardiovascular diseases and is regarded as a major contributing factor to hypertension. While the link between salt and hypertension is well established, the mechanisms by which high dietary salt intake leads to increased blood pressure remain unclear. Increases in plasma sodium are detected by specialized brain centers, causing an activation of neurons that secrete vasopressin (VP). VP is antidiuretic hormone that mediates water retention in the kidney and causes the constriction of blood vessels, contributing to the elevation of blood pressure. We propose to study the molecular mechanisms by which high salt intake leads to excessive secretion of VP, leading to hypertension. Our hypothesis is that high salt intake provokes inflammatory processes in specialized brain centers controlling VP neuron activity, leading to exaggerated activation of VP neurons. This, in turn, leads to enhanced VP secretion, fluid retention and vasoconstriction and thereby increases blood pressure. The proposed research program will elucidate the mechanisms modulating VP release in hypertension. A better understanding of how high salt intake alters mechanisms controlling VP secretion may therefore lead to novel approaches for treating hypertension.