FRIDAY, May 16 (HealthDay News) -- Administration of tetrahydrobiopterin (BH4) stopped progressive chamber dilation and reversed hypertrophy in mice that underwent proximal aortic constriction, suggesting it may be useful in treating advanced hypertrophic heart disease, according to research published in the May 20 issue of Circulation: Journal of the American Heart Association.
An L. Moens, M.D., of Johns Hopkins Medical Institutions in Baltimore, and colleagues analyzed data from male mice subjected to transverse aortic constriction. They were investigating whether using BH4, a cofactor for the three aromatic amino acid hydroxylases, could restore the coupling and function of nitric oxide synthase (NOS); its uncoupling during sustained pressure overload and the resulting stimulation of reactive oxygen species is thought to play a role in ventricular remodeling.
After four weeks of pressure overload, oral administration of BH4 for another five weeks in the mice reversed hypertrophy and fibrosis, recoupled endothelial NOS, lowered oxidant stress, and improved chamber and myocyte function, the researchers report. These factors in untreated mice worsened, they found.
"The present findings suggest that NOS-derived reactive oxygen species plays a particularly important role in decompensated hypertrophic heart disease. The existing clinical viability of BH4 as a drug, albeit for a different disorder at present, should help facilitate clinical translation and testing of the present findings to human heart disease. An intriguing potential patient population is individuals with heart failure and a preserved ejection fraction, often called diastolic heart failure," the authors conclude. "If the present findings can be translated to humans, BH4 might provide a novel and potent therapy to treat this common heart disease."
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