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 Ca(2+)-activated K(+) channels (BK(Ca)).


METHODS
The BK(Ca) 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 BK(Ca) channels and induces a large increase in the sensitivity of BK(Ca) channels to Ca(2+) of PA myocytes from normoxic and chronic hypoxic rats. Consequently, BK(Ca) 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.


CONCLUSIONS
Chronic inhalation of CO attenuates hypoxic pulmonary artery hypertension development presumably through activation of BK(Ca) 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.
Dubuis
Eric
E
LABPART, Faculté de Médecine, 2 bis Boulevard Tonnellé, 37032 Tours, France. dubuis@liv.ac.uk
Potier
Marie
M
Wang
Rui
R
Vandier
Christophe
C
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002248:Carbon Monoxide / Q000008:administration & dosage / Q000627:therapeutic use*; D016764:Cell Polarity / Q000187:drug effects; D002908:Chronic Disease; D004334:Drug Administration Schedule; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D000860:Hypoxia / Q000150:complications* / Q000503:physiopathology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D032342:Muscle Cells / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D010455:Peptides; D024681:Potassium Channels, Calcium-Activated; C064719:iberiotoxin; D002248:Carbon Monoxide; D002118:Calcium