Battle of the Sexes

Researcher Studies Gender Differences in Blood Pressure, Kidney Damage

While men and women both get high blood pressure and related kidney disease, the path to get there is shorter, steeper and just different for men, researchers say.

“They may end up at the same point, but the way they got there could be very different,” said Dr. Jennifer C. Sullivan, a pharmacologist/physiologist at MCG’s Vascular Biology Center.

“It’s known that men tend to develop hypertension earlier than women and the increase in blood pressure occurs more rapidly than it does in women, until they hit menopause. I look at our spontaneously hypertensive rats and see the same dichotomy in blood pressure,” Dr. Sullivan said of the animal model she studies.

“There are also differences in development of renal injury in the human population, and chronic renal disease seems to be worse in men. I see the same thing in my animal model.”

Dr. Sullivan, who recently received the 2007 New Investigator Award of the American Physiological Society’s Water and Electrolyte Homeostasis Section, is studying these gender differences to learn what protects premenopausal females.

Female hormones can’t account for all the difference, she said. “It’s not that easy. Men and women are more than just sex hormones.” When the rats’ testicles are removed, for example, blood pressure and injury incidence drop slightly; when ovaries are removed, blood pressure remains unchanged but kidney injury increases slightly.

 

“There are fundamental differences, I believe, in the physiology. They are going to end up at the same point, but the way there could be very different.”

She is comparing two major players in hypertension—vasoconstriction and levels of free radicals—in males and females.

She is finding that nitric oxide synthase (a molecule that signals smooth muscle cells to relax) may make more nitric oxide in females. Just how active an enzyme is depends on how it is phosphorylized, or turned on by adding phosphate groups. “Our preliminary data say that the phosphorylation status may increase nitric oxide production—and maintain kidney health—in females,” Dr. Sullivan said.

In contrast is the powerful constrictor of blood vessels, angiotensin 2. Males’ outer kidneys (the renal cortex) have ample AT1 receptors, enabling enables angiotensin 2 to do harm. “It’s a vasoconstrictor when it binds with AT1,” she said. “It will cause proliferation and hypertrophy, it can stimulate the production of reactive oxygen species, so it does all sorts of bad things.”

Fortunately, drugs are available to block angiotensin 2’s destructive action: angiotensin receptor blockers and ace inhibitors. Interestingly, clinical studies already have shown these drugs don’t work as well in women. “A lot of women are on these drugs, and I’m not sure it’s doing them a lot of good,” she said. One of her goals is to find out.

Males also have too many highly reactive and potentially damaging free radicals in the renal cortex. Free radicals or reactive oxygen species have important jobs in the body, but an excess creates oxidative stress, a contributor to most major diseases. In the case of high blood pressure, free radicals damage proteins critical to blood vessels and kidneys.

 

The body has natural mechanisms for keeping free radicals in check, including endogenous antioxidants. “But if you get increases, it can overwhelm the natural ability of the body to take care of it,” she said. When she looks at the toll on the kidneys, she finds about a 50 percent increase in the amount of protein excreted in the urine—a sure sign of kidney disease—in the males. She notes that by age 70, the rates of cardiovascular disease and hypertension are similar in men and women and that older women tend to have higher blood pressures than agematched men. Her work is funded in part by an American Heart Association Scientist Development Grant.

Toni Baker

 

The Medical College of Georgia is the state’s health sciences university with a tripartite mission of education, research and patient care.