Dual impact of a nitric oxide donor, GEA 3175, in human pulmonary smooth muscle |
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Authors: | Elmedal Britt Mulvany Michael J Simonsen Ulf |
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Affiliation: | Department of Pharmacology, University of Aarhus, 8000 Aarhus C, Denmark. |
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Abstract: | Nitric oxide (NO) donors could constitute an alternative to inhaled NO as treatment in some patients with pulmonary hypertension. Therefore, the present study investigated the relaxation mechanisms of a novel NO donor, 3-(3-chloro-2-methylphenyl)-5-[[4-methylphenyl)sulphonyl]amino]-)hydroxide (GEA 3175) in segments of human pulmonary arteries and bronchioles, which were mounted in microvascular myographs. GEA 3175 induced concentration-dependent relaxations and was more potent in pulmonary arteries than in bronchioles. A blocker of soluble guanylyl cyclase, 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ), and iberiotoxin, a blocker of large-conductance calcium-activated K channels, both reduced relaxations induced by GEA 3175 in pulmonary arteries and bronchioles. Combining of ODQ and iberiotoxin did not produce additional inhibition. GEA 3175 relaxation is mediated through guanylyl cyclase-dependent mechanisms followed by activation of large-conductance calcium-activated K(+) channels. The dilatation of both pulmonary small arteries and airways by GEA 3175 seems advantageous, if it is considered administered as inhalation therapy for pulmonary hypertension. |
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Keywords: | Human pulmonary artery Human bronchiole Nitric oxide donor Soluble guanylyl cyclase Large-conductance calcium-activated potassium channel |
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