Details

Autor(en) / Beteiligte

• Nozik-Grayck, Eva
• McMahon, Timothy J
• Huang, Yuh-Chin T
• Dieterle, Christine S
• Stamler, Jonathan S
• Piantadosi, Claude A

Titel

Pulmonary vasoconstriction by serotonin is inhibited by S-nitrosoglutathione

Ist Teil von

• American journal of physiology. Lung cellular and molecular physiology, 2002-05, Vol.282 (5), p.1057-L1065

Ort / Verlag

United States

Erscheinungsjahr

2002

Quelle

MEDLINE

Beschreibungen/Notizen

• Departments of Pediatrics and Medicine, Duke University Medical Center, Durham, North Carolina 27710 Nitric oxide (NO) functions as an endothelium-derived relaxing factor by activating guanylate cyclase to increase cGMP levels. However, NO and related species may also regulate vascular tone by cGMP-independent mechanisms. We hypothesized that naturally occurring NO donors could decrease the pulmonary vascular response to serotonin (5-HT) in the intact lung through chemical interactions with 5-HT 2 receptors. In isolated rabbit lung preparations and isolated pulmonary artery (PA) rings, 50-250 µM S -nitrosoglutathione (GSNO) inhibited the response to 0.01-10 µM 5-HT. The vasoconstrictor response to 5-HT was mediated by 5-HT 2 receptors in the lung, since it could be blocked completely by the selective inhibitor ketanserin (10 µM). GSNO inhibited the response to 5-HT by 77% in intact lung and 82% in PA rings. In PA rings, inhibition by GSNO could be reversed by treatment with the thiol reductant dithiothreitol (10 mM). 3-Morpholinosydnonimine (100-500 µM), which releases NO and O simultaneously, also blocked the response to 5-HT. Its chemical effects, however, were distinct from those of GSNO, because 5-HT-mediated vasoconstriction was not restored in isolated rings by dithiothreitol. In the intact lung, neither NO donor altered the vascular response to endothelin, which activates the same second-messenger vasoconstrictor system as 5-HT. These findings, which did not depend on guanylate cyclase, are consistent with chemical modification by NO of the 5-HT 2 G protein-coupled receptor system to inhibit vasoconstriction, possibly by S -nitrosylation of the receptor or a related protein. This study demonstrates that GSNO can regulate vascular tone in the intact lung by a reversible mechanism involving inhibition of the response to 5-HT. nitric oxide; G protein-coupled receptor