Aldosterone is a steroid hormone important to the regulation of salt, fluid and potassium in the body. Researchers at the “Metabolic and sex differences in aldosterone responses” symposium—presented today at the American Physiological Society (APS) Aldosterone and ENaC in Health and Disease: The Kidney and Beyond Conference in Estes Park, CO—will explore the growing body of research that finds sex is a major determinant of how aldosterone acts on the body.

More and more research into cardiovascular health is finding differences in how men and women regulate blood pressure. In addition to its role regulating salt and potassium, aldosterone also plays a vital role in regulating blood pressure and in the health of the heart and kidneys. It works by combining with structures called mineralocorticoid receptors, which are a common target for cardiovascular medication.

Featured symposium speakers will discuss what recent research is showing about the extent of these sex differences and how they may affect cardiovascular health.

José Romero, PhD, of Brigham and Women's Hospital and Harvard Medical School in Boston, will present research conducted in humans and rats that suggest “women may be more responsive to mineralocorticoid receptor blockade than men.” Human studies found women, especially premenopausal women, to have more robust blood pressure responses to changes in dietary salt than men. In rats, an increase in a compound that stimulates aldosterone production led to greater damage to the heart and kidneys in females than in males. And in sex-differentiated samples of aldosterone-producing cells, the female cells produced greater amounts of aldosterone when treated than male cells.

Fat-storage cells, called adipocytes, produce a hormone called leptin that is primarily known for its role in regulating hunger. Both males and females experience increased production of leptin along with an increase in cardiovascular disease. However, Eric J. Belin de Chantemèle, PhD, of the Medical College of Georgia at Augusta University, and his team have found that the mechanisms behind this obesity-related cardiovascular disease are differ significantly between the sexes. In men, leptin triggers high blood pressure by stimulating the sympathetic nervous system, part of the nervous system known for the “fight or flight response.” In women, leptin stimulated production of aldosterone, an excess of which led to cardiovascular dysfunction.

Mykola Mamenko, PhD, of Medical College of Georgia at Augusta University, will discuss his team’s finding of sex-specific sensitivity to aldosterone in the regulation of high blood pressure. The researchers treated male and female rats with a compound that stimulates aldosterone and then treated some of those rats with the medication spironolactone, which is used to treat high blood pressure. They found that, although the aldosterone stimulant increased aldosterone in both sexes, spironolactone only improved blood pressure in females. Further metabolic measures reiterated this effect, showing that spironolactone only improved in kidney function in females.

Following up on previous research on a high-salt diet, Jessica Faulkner, PhD, of the Medical College of Georgia at Augusta University, and her team investigated sex-differences in response to a low-salt diet. They fed male and female mice either a normal- or low-salt diet. They then measured markers of cardiovascular response at 14 and 28 days. Female mice on a low-salt diet showed greater production of aldosterone and greater levels of an enzyme involved in aldosterone production than males.