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Arginine Therapy

A New Treatment for Pulmonary Hypertension in Sickle Cell Disease?

Departments of Emergency Medicine and Hematology/Oncology and Pediatric Clinical Research Center, Children's Hospital and Research Center at Oakland, Oakland; Department of Hematology, University of California at San Francisco, San Francisco; Children's Hospital, Oakland Research Institute, Oakland, California; and Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Correspondence and requests for reprints should be addressed to Claudia R. Morris, M.D., Department of Emergency Medicine, Children's Hospital Oakland, 747 52nd Street, Oakland, CA 94609. E-mail: cmorris{at}mail.cho.org

Pulmonary hypertension is a life-threatening complication of sickle cell disease. L-Arginine is the nitrogen donor for synthesis of nitric oxide, a potent vasodilator that is deficient during times of sickle cell crisis. This deficiency may play a role in pulmonary hypertension. The enzyme arginase hydrolyzes arginine to ornithine and urea, and thus, it may compete with nitric oxide synthase, leading to decreased nitric oxide production. Nitric oxide therapy by inhalation has improved pulmonary hypertension associated with acute chest syndrome in sickle cell disease, and several studies demonstrate therapeutic benefits of arginine therapy for primary and secondary pulmonary hypertension. We sought to determine the effects of arginine therapy on pulmonary hypertension in patients with sickle cell disease. Arginase activity was also determined. Oral arginine produced a 15.2% mean reduction in estimated pulmonary artery systolic pressure (63.9 ± 13 to 54.2 ± 12 mm Hg, p = 0.002) after 5 days of therapy in 10 patients. Arginase activity was elevated almost twofold (p = 0.07) in patients with pulmonary hypertension and may limit arginine bioavailability. With limited treatment options and a high mortality rate for patients with sickle cell disease who develop pulmonary hypertension, arginine is a promising new therapy that warrants further investigation.

Key Words: pulmonary hypertension • L-arginine • nitric oxide • sickle cell disease • arginase

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