The study examined the effect of N-acetylcysteine (NAC) and the results, published in this month's issue of the Journal of Clinical Investigation, indicate the antioxidant can form a red blood cell-derived molecule that makes blood vessels think they are not getting enough oxygen. This can lead to pulmonary arterial hypertension (PAH), a condition characterized by high blood pressure in the arteries carrying blood to the lungs. While no one appears to be ringing any alarm bells, the researchers say the next step is to determine whether or not the effect on mice is reproduced in humans. The researchers claim to have uncovered a new understanding of the way oxygen is sensed by the body and the chemical reactions that take place as a result. "We were really surprised," said Dr. Ben Gaston, UV Children's Hospital paediatrician and study leader. As part of the study, NAC and nitrosothiols were administered to mice for three weeks. The NAC was converted by red blood cells into the nitrosothiol called S-nitroso-N-acetylcysteine (SNOAC). The 'normal' mice that received NAC and SNOAC developed PAH. Mice missing an enzyme known as endothelial nitric oxide synthase were protected from the adverse effects of NAC, but not SNOAC. These mice had not converted NAC to SNOAC, thereby suggesting NAC must be converted to SNOAC to cause PAH. "NAC fools the body into thinking that it has an oxygen shortage," said Gaston. "We found that an NAC product formed by red blood cells, know as a nitrosothiol, bypasses the normal regulation of oxygen sensing. It tells the arteries in the lung to 'remodel'; they become narrow, increasing the blood pressure in the lungs and causing the right side of the heart to swell." The researchers were able to isolate the way the body responds to nitrosothiols. According to Gaston, these are made when a decreased amount of oxygen is being carried by red blood cells and the response is not in fact to the amount of oxygen dissolved in the blood. The team says it is now necessary to determine the threshold past which antioxidant use may be detrimental to heart or lung functioning. The researchers are calling for health practitioners to check patients for PAH. NAC is being tested in clinical trials for patients with conditions such as cystic fibrosis. As well, clinical trials on nitrosothiols are being planned, according to Gaston. NutraIngredients had not seen the published study prior to publication of this article.