Journal article

Publication year: 2016

Pages: 271-281

Journal: Journal of Applied Physiology

Volume number: 120

Issue number: 2

ISSN: 8750-7587

eISSN: 1522-1601

Open access status: Bronze

DOI Link: https://doi.org/10.1152/japplphysiol.00726.2015

Publisher: American 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.

Harvard Citation style: Pak, 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 Citation style: Pak, 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