The transition to life outside the womb doesn't always go smoothly. Complications during birth can send an infant into respiratory distress, which can worsen to a severe condition called persistent pulmonary hypertension of the newborn (PPHN).
The condition is common, affecting about one in 500 newborns, said Dr. Marshall L. Summar, associate professor of Pediatrics in the division of Medical Genetics and Molecular Physiology & Biophysics. Summar, Dr. DeLinda Pearson, a fellow in Neonatology, and colleagues have now discovered a link between the ability to generate the compound nitric oxide and development of PPHN. Their findings, reported June 14 in the New England Journal of Medicine, suggest strategies to prevent the life-threatening pulmonary hypertension in at-risk newborns.
At the center of the story is nitric oxide, a compound that reduces blood pressure and is used to treat infants with PPHN. In the body, nitric oxide is synthesized from the amino acid arginine. Summar theorized that low supplies of arginine and its precursor citrulline would result in low supplies of nitric oxide, and that these conditions might predispose an infant to PPHN.
His reasons for wondering about the effects of low arginine supplies were rooted in over 12 years of research focused on the urea cycle, a metabolic pathway that rids the body of waste nitrogen. Arginine is an intermediate product of the urea cycle, and Summar and colleagues had identified genetic variants in the urea cycle enzyme carbamyl phosphate synthetase I (CPSI) that reduce the amount of arginine produced. PPHN, he thought, represented a condition where the genetic changes might make a difference.
Summar and Pearson collaborated with Dr. William F. Walsh, professor of Pediatrics and director of Nurseries, Dr. Brian W. Christman, associate professor of Medicine, and Sheila Dawling, Ph.D., associate professor of Pathology, to test this idea. They enrolled 65 near-term newborns with respirato
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Contact: John Howser
john.howser@mcmail.vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
13-Jun-2001