Blunted effect of the Kv channel inhibitor on pulmonary circulation in Tibetan sheep: A model for studying hypoxia and pulmonary artery pressure regulation

Objective:   The aim of this study was to assess the effect of 4‐aminopyridine, a Kv channel inhibitor, on the pulmonary circulation of Tibetan sheep. It has been reported that chronic hypoxia downregulates the 4‐aminopyridine (4AP)‐sensitive Kv channel (which governs the membrane potential (Em) of...

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Published in:Respirology (Carlton, Vic.) Vic.), 2004-03, Vol.9 (1), p.125-129
Main Authors: Ishizaki, Takeshi, Sakai, Akio, Koizumi, Tomonori, Ruan, Zonghai, Wang, Zhan Gang
Format: Article
Language:English
Subjects:
4-aminopyridine
4-Aminopyridine - pharmacology
Altitude
Animals
Atmosphere Exposure Chambers
Disease Models, Animal
high-altitude active sheep
Hypoxia
Kv channel
Male
Potassium Channel Blockers - pharmacology
pulmonary circulation
Pulmonary Circulation - drug effects
pulmonary hypertension
Sheep
Vasodilation - drug effects
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Summary:Objective:   The aim of this study was to assess the effect of 4‐aminopyridine, a Kv channel inhibitor, on the pulmonary circulation of Tibetan sheep. It has been reported that chronic hypoxia downregulates the 4‐aminopyridine (4AP)‐sensitive Kv channel (which governs the membrane potential (Em) of pulmonary vascular smooth muscle cells in pulmonary vessels) without a change in 4AP sensitivity. Methodology:   Pulmonary haemodynamic indices and blood gas analyses were measured in six young male animals in an altitude chamber that was adjusted to simulated altitudes of 0 m, 2260 m, and 4500 m. Drip infusion of 4AP, 10 mg/h for 3 h, was started and continued during the study. Results:   With the increase in altitude mean pulmonary artery pressure increased and mean Pao2 decreased. 4AP had no effect on the levels of mean PPA, mean pulmonary artery wedge pressure, cardiac output, and mean PaO2, mean PaCO2, and mean pH at any altitude but tended to alter heart rate and mean arterial pressure at altitudes of 2260 m and 4500 m. Conclusion:   It is concluded that the 4AP‐sensitive Kv channel does not play a role in pulmonary vascular tone in high‐altitude active Tibetan sheep. Their pulmonary vascular oxygen sensing appears not to involve Kv channels.
ISSN:1323-7799
1440-1843
DOI:10.1111/j.1440-1843.2003.00531.x