Copyright © 2004, European Society of Cardiology
Continuous inhalation of carbon monoxide attenuates hypoxic pulmonary hypertension development presumably through activation of BKCa channels
aLABPART, Faculté de Médecine, 2 bis Boulevard Tonnellé, 37032 Tours, France
bDepartment of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, Canada SK, S7N 5E5
* Corresponding author. Present address: University of Liverpool, Department of Physiology, Crown Street, L69 3BX, Liverpool, UK. Tel.: +44 151 706 4067 or +44 151 706 4031; fax: +44 151 794 5327. Email address: dubuis{at}liv.ac.uk
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 gasotransmitter, nitric oxide.
KEYWORDS Pulmonary artery hypertension; Calcium-activated potassium channel; Carbon monoxide; Chronic hypoxia
1 Present address: INSERM E-0211 Nutrition, Croissance, Cancer, Faculté de Médecine, 2 bis Boulevard Tonnellé, 37032 Tours, France.
Time for primary review 27 days
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