Journalartikel

Effects of carbon monoxide-releasing molecules on pulmonary vasoreactivity in isolated perfused lungs


AutorenlistePak, Oleg; Bakr, Adel G.; Gierhardt, Mareike; Albus, Julia; Strielkov, Ievgen; Kroschel, Florian; Hoeres, Timm; Hecker, Matthias; Ghofrani, Hossein A.; Seeger, Werner; Weissmann, Norbert; Sommer, Natascha

Jahr der Veröffentlichung2016

Seiten271-281

ZeitschriftJournal of Applied Physiology

Bandnummer120

Heftnummer2

ISSN8750-7587

eISSN1522-1601

Open Access StatusBronze

DOI Linkhttps://doi.org/10.1152/japplphysiol.00726.2015

VerlagAmerican Physiological Society


Abstract
In addition to its renowned poisonous effects, carbon monoxide (CO) is being recognized for its beneficial actions on inflammatory and vasoregulatory pathways, particularly when applied at low concentrations via CO-releasing molecules (CO-RMs). In the lung, CO gas and CO-RMs are suggested to decrease pulmonary vascular tone and hypoxic pulmonary vasoconstriction (HPV). However, the direct effect of CO-RMs on the pulmonary vasoreactivity in isolated lungs has not yet been investigated. We assessed the effect of CORM-2 and CORM-3 on the pulmonary vasculature during normoxia and acute hypoxia (1% oxygen for 10 min) in isolated ventilated and perfused mouse lungs. The effects were compared with those of inhaled CO gas (10%). The interaction of CORM-2 or CO with cytochrome P-450 (CYP) was measured simultaneously by tissue spectrophotometry. Inhaled CO decreased HPV and vasoconstriction induced by the thromboxane mimetic U-46619 but did not alter KCl-induced vasoconstriction. In contrast, concentrations of CORM-2 and CORM-3 used to elicit beneficial effects on the systemic circulation did not affect pulmonary vascular tone. High concentration of CO-RMs or long-term application induced a continuous increase in normoxic pressure. Inhaled CO showed spectral alterations correlating with the inhibition of CYP. In contrast, during application of CORM-2 spectrophotometric signs of interaction with CYP could not be detected. Application of CO-RMs in therapeutic doses in isolated lungs neither decreases pulmonary vascular tone and HPV nor does it induce spectral alterations that are characteristic of CO-inhibited CYP. High doses, however, may cause pulmonary vasoconstriction.



Zitierstile

Harvard-ZitierstilPak, O., Bakr, A., Gierhardt, M., Albus, J., Strielkov, I., Kroschel, F., et al. (2016) Effects of carbon monoxide-releasing molecules on pulmonary vasoreactivity in isolated perfused lungs, Journal of Applied Physiology, 120(2), pp. 271-281. https://doi.org/10.1152/japplphysiol.00726.2015

APA-ZitierstilPak, O., Bakr, A., Gierhardt, M., Albus, J., Strielkov, I., Kroschel, F., Hoeres, T., Hecker, M., Ghofrani, H., Seeger, W., Weissmann, N., & Sommer, N. (2016). Effects of carbon monoxide-releasing molecules on pulmonary vasoreactivity in isolated perfused lungs. Journal of Applied Physiology. 120(2), 271-281. https://doi.org/10.1152/japplphysiol.00726.2015



Schlagwörter


carbon monoxide-releasing molecule-2carbon monoxide-releasing molecule-3HYPOXIC PULMONARY VASOCONSTRICTIONK-CA CHANNELSVASOCONSTRICTION


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