Grant: Project Grant

Hypertension is the prevalent treatable risk factor contributing to cardiovascular diseases, which remain the most common cause of death in industrialized countries taking the lives of over one million people every year in the U.S. alone. In Canada, over 20% of adults are diagnosed with hypertension, and an estimated 9 in 10 people who live an average lifespan will develop the condition in their lifetime. Excessive dietary salt intake is strongly correlated with cardiovascular diseases such as myocardial infarction and stroke, 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 salt intake leads to increased blood pressure remain unclear. Consumption of salt in a meal increases the levels of salt (sodium) in the blood, causing activation of specialized brain cells that release a hormone called vasopressin. Vasopressin leads to retention of water in the kidney in order to decrease blood sodium levels back to normal. Vasopressin also affects blood vessels causing them to constrict. These effects of vasopressin can lead to the elevation of blood pressure. Our hypothesis is that chronic exposure to excessive amounts of salt causes a hyperactivation of vasopressin-secreting brain cells. These cells have a specialized cellular skeleton that determine their shape (just like the shape of the body is determined by its skeleton). This cellular skeleton becomes denser and stiffer when the cells are chronically exposed to high salt levels. As a result, the cells become overly activated and secrete excessive amounts of vasopressin, leading to a sustained blood pressure increase and hypertension. We propose to study the mechanisms by which high salt causes the modification of cellular skeleton in the brain cells thereby leading to hypertension.