Continuous inhalation of carbon monoxide attenuates hypoxic pulmonary hypertension development presumably through activation of BKCa channels

Objective: We tested the hypothesis that inhalation of a low concentration of exogenous carbon monoxide (CO) attenuates the development of hypoxic pulmonary artery hypertension by activation of large-conductance voltage and Ca2+-activated K+ channels (BKCa). Methods: The BKCa activity was measured using whole-cell and inside-out patch clamp recordings in Wistar rat pulmonary artery (PA) myocytes. Pulmonary artery pressures were measured in vivo and membrane potentials were recorded in vitro in pressurized resistance arteries. Results: Chronic CO inhalation slightly increases single-channel conductance of BKCa channels and induces a large increase in the sensitivity of BKCa channels to Ca2+ of PA myocytes from normoxic and chronic hypoxic rats. Consequently, BKCa currents are increased and play a more prominent role in controlling resting membrane potential of PA myocytes. Chronic CO inhalation also reduces hemodynamic changes induced by chronic hypoxia and attenuates hypoxic pulmonary artery hypertension. Conclusion: Chronic inhalation of CO attenuates hypoxic pulmonary artery hypertension development presumably through activation of BKCa channels. These results highlight the potential use of CO as a novel avenue for research on the treatment of pulmonary artery hypertension (PAHT) in a similar manner to another gasotransimitter, nitric oxide. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.