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Am J Physiol Heart Circ Physiol 285: H2327-H2335, 2003. First published July 3, 2003; doi:10.1152/ajpheart.00507.2003
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Bicarbonate-dependent superoxide release and pulmonary artery tone

Eva Nozik-Grayck, Yuh-Chin T. Huang, Martha Sue Carraway, and Claude A. Piantadosi

Departments of Pediatrics and Medicine, Duke University Medical Center, Durham, North Carolina 27710

Submitted 2 June 2003 ; accepted in final form 2 July 2003

Pulmonary vasoconstriction is influenced by inactivation of nitric oxide (NO) with extracellular superoxide (). Because the short-lived anion cannot diffuse across plasma membranes, its release from vascular cells requires specialized mechanisms that have not been well delineated in the pulmonary circulation. We have shown that the bicarbonate anion exchange protein (AE2) expressed in the lung also exchanges for . Thus we determined whether release involved in pulmonary vascular tone depends on extracellular . We assessed endothelium-dependent vascular reactivity and release in the presence or absence of in pulmonary artery (PA) rings isolated from normal rats and those exposed to hypoxia for 3 days. Lack of extracellular in normal PA rings significantly attenuated endothelial release, opposed hypoxic vasoconstriction, and enhanced acetylcholine-mediated vasodilation. Release of was also inhibited by an AE2 inhibitor (SITS) and abolished in normoxia by an NO synthase inhibitor (NG-nitro-L-arginine methyl ester). In contrast, hypoxia increased PA AE2 protein expression and release; the latter was not affected by NG-nitro-L-arginine methyl ester or other inhibitors of enzymatic generation. Enhanced release by uncoupling NO synthase with geldanamycin was attenuated by hypoxia or by elimination. These results indicate that produced by endothelial NOS in normoxia and unidentified sources in hypoxia regulate pulmonary vascular tone via AE2.

anion exchange protein; nitric oxide; endothelial nitric oxide synthase; hypoxia



Address for reprint requests and other correspondence: E. Nozik-Grayck, Box 3046, Dept. of Pediatrics, Duke Univ. Medical Center, Durham, NC 27710 (E-mail: grayc001{at}mc.duke.edu).




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