High Blood Pressure Linked to Nitric Oxide Production in White, But Not Black, Preemies Receiving Steroids, UB Study Finds

BUFFALO, N.Y -- Studying why premature infants develop high blood pressure after receiving steroids to aid their lung function, University at Buffalo neonatologists found that steroids interfere with production of nitric oxide (NO), a critical biological component known to relax blood vessels and reduce blood pressure.

However, the relationship appeared only in white infants. Furthermore, the study revealed for the first time that white infants normally produce more nitric oxide than black infants.

This finding may help explain why blacks suffer more essential hypertension than whites as adults, said Vaddarse N. Nagaraja, M.D., UB assistant professor of pediatrics and lead author on the study.

Nagaraja and colleagues presented results of the study May 5 at the Pediatric Academic Societies meeting in Seattle.

The steroid drug dexamethasone has been used routinely to treat chronic lung disease in premature infants, with high blood pressure a common side effect. Studies of steroids using an animal model had shown that the medications reduced the animal's production of nitric oxide, but no studies had been done in the infants themselves on the relationship between a decrease in NO and blood pressure rise.

This prospective study involved 25 infants who were hospitalized in the intensive care unit of Women and Children's Hospital in Buffalo during 2001 and who were due to receive three days of steroid therapy.

Three blood-pressure readings were taken at one-hour intervals before steroids were administered, and during the three days of treatment.

To determine if there was an effect on NO production, researchers used the end products of NO metabolism -- urinary nitrates -- as a marker of NO production, taking samples of urine before and after the treatment period.

Results showed that overall, blood pressure increased significantly in infants after three treatment days, while urinary nitrates decreased. Most surprisingly, when results were analyzed by race, the increase in blood pressure was linked to a decrease in NO production only in white infants.

As blood pressure rose, NO production, as measured by urinary nitrates, fell by 38 percent on average in white infants. Blood pressure increased similarly in the black infants, but NO production remained essentially unchanged. Moreover, white infants showed higher levels of NO production at the study start.

"We don't know what accounts for the rise in blood pressure in black infants receiving steroids." said Nagaraja. "We will have to keep searching."

While the American Academy of Pediatrics in March 2002 issued a statement discouraging extensive use of steroids in premature infants because of some observed adverse neurological effects, they still are used in certain situations.

"The effect of steroids on nitric oxide production is another reason to be cautious concerning their use," Nagaraja said.

Also contributing to the study were Satyan Lakshminrusimha, M.D., James A. Russell, M.D., and Rita M. Ryan, M.D., all from Department of Pediatrics in the UB School of Medicine and Biomedical Sciences; Sylvia Gugino of the UB Department of Physiology and Biophysics, where Russell also holds an appointment, and Robin H. Steinhorn, M.D., formerly of UB, now at Northwestern University.