Grant: Operating Grant

Hypertension (high blood pressure) affects more than 1 billion people worldwide (~25-30% of population) and contributes to approximately 7million cardiovascular deaths/year (such as heart attack, stroke with paralysis). Excess production by the adrenal glands of a hormone called aldosterone causes salt retention by the kidneys, increased blood volume and high blood pressure; this is called primary aldosteronism. It is responsible for 6-12% of hypertension in humans and would thus affect almost 3% of the population. Primary aldosteronism carries for affected patients 5-10 times higher risks of stroke, heart attack and other cardiovascular risks than the most common form of high blood pressure called essential hypertension. The mechanisms causing the development or unilateral or bilateral tumors or increased size (hyperplasia) of the adrenal glands responsible for primary aldosteronism are poorly understood. Our group and other researchers have recently found that the abnormal presence and function of several hormone receptors (like a lock in a door that the hormone opens if it is the good key) in affected adrenal tissues are responsible for the increased secretion of aldosterone in this disease independently from its normal control mechanisms. Our proposed studies will clarify the role of this abnormal regulation of aldosterone by various hormone receptors. They will be conducted in patients affected by this disease and compared to normal individuals. In addition we will study adrenal tumors after removal by surgery and the adjacent adrenal tissue We expect to improve the diagnosis of this important cause of hypertension. Identification of aberrant hormone receptors should allow new treatments by drugs capable of blocking those receptors. This should result in normalisation of blood pressure but also in the reversal of the increased risk of cardiovascular events in individuals affected by primary aldosteronism.