Involvement of tetrahydrobiopterin in local change of endothelium-dependent vasorelaxation in pulmonary hypertension

A deficiency of tetrahydrobiopterin (BH4), a NO-synthase co-factor, results in reactive oxygen species synthesis by NO-synthase. It leads to disturbances of endothelium-dependent vasorelaxation. We performed our study on the monocrotaline model of pulmonary hypertension. A decrease in endothelium-de...

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Bibliographic Details
Published in:	Rossiiskii fiziologicheskii zhurnal imeni I.M. Sechenova Vol. 89; no. 12; p. 1516
Main Authors:	Davydova, M P, Postnikov, A B, D'iakonov, K B, Liubitskiĭ, O B, Medvedeva, H A
Format:	Journal Article
Language:	Russian
Published:	Russia (Federation) 01-12-2003
Subjects:	Animals Biopterins - analogs & derivatives Biopterins - metabolism Biopterins - pharmacology Disease Models, Animal Endothelium, Vascular - drug effects Endothelium, Vascular - metabolism Hypertension, Pulmonary - chemically induced Hypertension, Pulmonary - metabolism Hypertension, Pulmonary - physiopathology Lung - blood supply Lung - drug effects Lung - metabolism Male Monocrotaline - toxicity Nitric Oxide Synthase - metabolism Oxygen - metabolism Pulmonary Artery - drug effects Pulmonary Artery - metabolism Rats Rats, Wistar Vasoconstrictor Agents - pharmacology Vasodilation - drug effects Vasodilation - physiology Vasodilator Agents - pharmacology
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Summary:	A deficiency of tetrahydrobiopterin (BH4), a NO-synthase co-factor, results in reactive oxygen species synthesis by NO-synthase. It leads to disturbances of endothelium-dependent vasorelaxation. We performed our study on the monocrotaline model of pulmonary hypertension. A decrease in endothelium-dependent relaxation was observed only in intrapulmonary arteries of monocrotaline-treated rats. A perfusion of BH4 (0.1 mol/liter) increased significantly endothelium-dependent dilation of hypertensive pulmonary arteries (p < 0.01). But BH4 did not influence the relaxation of systemic vessels and the dilation responses of pulmonary and systemic arteries of control rats. Measuring of superoxide by lucigenin-mediated chemiluminescence showed five-fold O2- production in intrapulmonary arteries of pulmonary hypertensive rats, that was activated by acetylcholine and inhibited by a nonselective NO-synthase blocker (L-NAME). However, activity of NO-synthase measured as [H3]arginine to [H3]citrulline conversion and assessed in pulmonary vessels and aortic tissue, did not differ in control and monocrotaline-treated groups. These data suggest, that there is a local deficiency of BH4--in pulmonary vessels, without significant changes of systemic circulation.
ISSN:	0869-8139