Sex differences in response to vasoactive substances in early uncontrolled diabetes

Aug 17 2007

Diabetes is associated with the development of vascular (blood vessel) disease. As we age, vascular disease becomes more common.

It has been thought that females may be more susceptible to the earlier development of vascular disease, as vascular changes are observed in females long before any significant development occurs in males. Now, a team of Georgetown University researchers has determined that the vascular activities in diabetic animals vary according to sex. This discovery may eventually have implications for the way males and females are treated medically in the future.

The study, entitled "Sex Differences in Response to Vasoactive Substances in Early Uncontrolled Diabetes," was conducted by Adam Mitchell, Adam Myers and Susan Mulroney, all of the Department of Physiology and Biophysics, Georgetown University, Washington, DC. Mr. Mitchell presented the status of the team's findings at the conference, Sex and Gender in Cardiovascular-Renal Physiology and Pathophysiology. The meeting, sponsored by the American Physiological Society (APS; www.The-APS.org), was held August 9-12, 2007 in Austin, TX.

The researchers examined the notion that very early changes in artery activity exists in diabetic animals and differ by sex. To test their hypothesis they divided adult male and female rats into three groups. The first group (control) received no treatment. The second group received streptozotocin (STZ) to induce diabetes. The third group received STZ plus growth hormone (GH), which is thought to exacerbate disease progression in diabetes.

After eight weeks, the vascular reactivity to phenylephrine, which increases blood pressure, and acetylcholine, which reduces blood pressure, was measured in the vessels from the animals. Vascular response to these substances was also observed during exposure to L-NAME (which blocks production of nitric oxide, a potent artery relaxer) and neuropeptide Y (which augments the restriction of blood vessels).

The investigators found that:

in the early stage of the disease, both male and female diabetics experienced significant decreases in the reactivity (i.e., how responsive the vessel is to a drug) of their blood vessels when exposed to acetylcholine. This occurred independent of the GH injections.

while female diabetic rats had an increased response to phenylephrine, there was no such change among their male counterparts.

female controls had a larger change in phenyleprine reactivity in the presence of L-NAME than did diabetic females, indicating that the diabetic females had a reduced level of nitric oxide, which dilates the artery and increases blood flow.

diabetic males had the opposite reaction of diabetic females when exposed to phenylephrine and L-NAME. The diabetic males also produced more nitric oxide than did their controls.

all diabetic rats exposed to growth hormone showed an increase in nitric oxide, regardless of gender.

The findings support the researchers hypothesis of the existence of sex-related changes in vascular activity in diabetic animals. While the production of NO is significantly altered in the diabetic rats, the results show that gender and the presence of GH greatly contribute to this vascular dysfunction. According to Mitchell, "These findings show the importance of sex differences to understanding development of vascular problems early in diabetes and has implications on potential sex-specific therapeutic intervention."