Understanding how adrenal nodules can cause drug resistant hypertension

Do somatic mutations of an L-type Ca++ channel in aldosterone-producing adenomas of the adrenal indicate a novel mechanism and target for regulating aldosterone production? (Ms Sumedha Garg)

High blood pressure is a major risk factor that can lead to heart attacks and strokes. In around 10% of patients, high blood pressure occurs because their adrenal gland produces too much of a hormone called aldosterone – this condition is called hyperaldosteronism. These patients often respond poorly to blood pressure lowering drugs, so we need to find new ways to treat them. Recently Professor Morris Brown and his team at the University of Cambridge found that many of these patients have nodules in their adrenal glands that produce aldosterone in large amounts. One type of nodule was linked to alterations in a gene that related to a calcium channel called Cav1.3. They also identified a number of other unexpected genes and proteins that may control how much calcium enters cells and how groups of cells in the adrenal gland talk to each other. If the team can work out whether and how calcium in the cells leads to aldosterone production, and therefore high blood pressure, these genes and proteins could ultimately be targets for new drugs for these patients. Professor Brown has been awarded a PhD studentship to investigate the underlying mechanisms of aldosterone production in the adrenal gland. The student will use tissue and cells from patients who have had adrenal surgery and will test whether the altered Cav1.3 channel boosts aldosterone production by adrenal cells, and whether new or existing drugs that block Cav1.3 can block aldosterone secretion. The researchers believe the nodules have to be intact for aldosterone secretion to be controlled properly. The student will look into whether or not ‘scaffolding’ proteins that keep the nodule intact are important for controlling aldosterone secretion. By improving our understanding of aldosterone secretion in the adrenal gland, this research may reveal new ways to treat high blood pressure in people with hyperaldosteronism.