Grant: Project Grant

Hypertension, or high blood pressure, is the leading cause of cardiovascular disease and premature death and disability in industrialized countries. Hypertension affects about 1 in 4 Canadians aged 20 to 79, and is the leading risk factor for death globally. Despite increasing awareness and wider availability of anti-hypertensive medications, the prevalence of hypertension remains stable, including in the younger population group aged 20-39. Excessive dietary salt intake is the major lifestyle risk factor associated with hypertension, and is strongly correlated with cardiovascular diseases such as myocardial infarction and stroke. 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 of 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 dietary salt modify cellular skeleton in the brain cells thereby leading to hypertension.