When women are hypertensive their physicians should consider measuring their level of aldosterone, a hormone that at high levels damages the cardiovascular system, scientists say.

If aldosterone levels are high, they should consider prescribing drugs that directly target the hormone’s receptor, says Dr. Eric Belin de Chantemele, physiologist in the Vascular Biology Center and associate professor in the Department of Medicine at the Medical College of Georgia at Augusta University.

“We are finding more evidence that higher aldosterone levels in women translate to higher blood pressure and that the most effective way to treat hypertensive women likely is to target this hormone and its receptor,” Belin de Chantemele said, referencing what appears to be another clear distinction emerging between men and women.

At baseline, women have more aldosterone than men and those levels are known to soar in the face of obesity and diabetes. Now there is increasing evidence that aldosterone is a major driver of hypertension, potentially in women of any girth.

Belin de Chantemele notes that clinical studies already have provided some evidence that mineralocorticoid receptor blockers, like the old hypertensive agent spironolactone, work better at reducing blood pressure and cardiovascular risk in women than men.

Still it’s often only when other drugs fail, that drugs that directly affect aldosterone by blocking its receptor are tried. Rather mineralocorticoid receptor blockers, which work as a diuretic, are more commonly used as part of a cocktail for heart failure.

Aldosterone became a focus in Belin de Chantemele’s lab about five years ago while he was studying both male and female mice that were hypersensitive to the well–known satiety hormone leptin. While both sexes developed hypertension, as the scientists expected, they saw the so–called fight or flight mechanism, the sympathetic nervous system, had increased activation in the males, which they also expected. Leptin is well known to activate the sympathetic nervous system.

But sympathetic activity was not increased in the females. That begged the question: What was driving their hypertension?

“What we observed is that their aldosterone level was sky high,” says Belin de Chantemele. While aldosterone also has a positive role in regulating blood pressure, high levels of the steroid hormone are associated with many things that are bad for the cardiovascular system like inflammation and blood vessel stiffness and scarring.

They took a step back and examined the enzyme producing aldosterone, CYP11B2, and found it was also very high in the females. As they began to put the pieces together, they realized that it was leptin that was a direct regulator of the increased aldosterone production by the adrenal gland in the female mice.

In the face of high leptin levels, and as with obese humans, the brains of the obese mice were no longer listening to leptin’s message to stop eating and start burning fat. But MCG scientists found that their cardiovascular system was listening to leptin.

When the researchers blocked either leptin or mineralocorticoid receptors, blood pressure and endothelial cell function improved in both obese and leptin–sensitive mice, another confirmation of the leptin–aldosterone connection and the therapeutic potential of disconnecting aldosterone from its receptor.

Drugs like ACE inhibitors likely do have an indirect impact on aldosterone – angiotensin for example also regulates aldosterone.

Mineralocorticoid receptor blockers often are not prescribed to men because a side effect can include an increase in breast size, he notes.