Inflammatory Genes Linked to Hypertension

Mounting evidence suggests that inflammation, a part of the immune response implicated in diseases such as cancer, Alzheimer’s and diabetes, may also help translate stress into high blood pressure.

“There is a concept that hypertension is an inflammatory condition,” said Dr. Haidong Zhu, an MCG molecular geneticist who believes the connection lies in the kidneys’ ability to release sodium.

When stress activates the sympathetic nervous system (the fightorflight mechanism), the body increases production of interleukin 6, a proinflammatory factor, which ultimately leads to production of other inflammatory factors such as C reactive protein.

Stress also prompts the body to retain sodium to help temporarily raise blood pressure, said Dr. Gregory Harshfield, director of MCG’s Georgia Prevention Institute and an expert on what happens when the body doesn’t let go afterward. He has documented the condition, called impaired stressinduced pressure natriuresis, in otherwise healthy teens.

 

Dr. Zhu suspects the condition may be caused by mutations in four sets of stressactivated inflammatory genes: interleukin 6, interleukin 6 receptor, cytokine signal transducer and Creactive protein.

Her research team, funded by a twoyear, $300,000 National Heart, Lung and Blood Institute Grant, is seeking variations of the genes in 500 teens with normal blood pressure. The teens, already enrolled in GPI studies measuring the effects of stress on the cardiovascular system, were put on a diet for four days to regulate sodium intake, then came to the GPI where they rested for an hour, played a racing video game for an hour, then rested for an hour.

Blood and urine samples were taken throughout the period. For this study, researchers will also collect DNA material from as many parents as possible to confirm their findings.

Pilot data indicate that black teens with normal blood pressure and a certain variation of the interleukin 6 gene have significantly reduced sodium excretion in the urine following stress.

Researchers have further implicated the inflammatory factor’s role in blood pressure regulation by showing that following stress, circulating levels of interleukin 6 rise and are still up an hour after the stressor is gone.

Dr. Zhu suspects that even without the genetic variations, inflammation affects blood pressure under stress, so she will study its impact alone and in concert with the mutations.

“Our longterm goal is to be able to identify a subgroup of individuals with a certain genetic profile that has an increased risk of developing high blood pressure in a stressful environment,” said Dr. Zhu.

 

If successful, those with saltsensitive hypertension—which includes approximately half of Americans with high blood pressure—might benefit from a lowsalt diet, exercise and antiinflammatory drugs.

The relationship between inflammation and high blood pressure, including how cytokines affect blood pressure, also is the subject of a fiveyear, $11 million National Heart, Lung and Blood Institute Program Project study at MCG led by Dr. R. Clinton Webb, chair of the Department of Physiology.

Toni Baker