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 pulmonary vascular smooth muscle cells in pulmonary vessels) without a change in 4AP sensitivity.


METHODS
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 PaO(2) decreased. 4AP had no effect on the levels of mean PPA, mean pulmonary artery wedge pressure, cardiac output, and mean PaO(2), mean PaCO(2), and mean pH at any altitude but tended to alter heart rate and mean arterial pressure at altitudes of 2260 m and 4500 m.


CONCLUSIONS
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.
School of Medicine, Fukui Medical University, Fukui, Japan. takeshi@fmsrsafukui-med.ac.jp
Takeshi
T
Ishizaki
Akio
A
Sakai
Tomonori
T
Koizumi
Zonghai
Z
Ruan
Zhan Gang
ZG
Wang
D015761:4-Aminopyridine / Q000494:pharmacology*; D000531:Altitude; D000818:Animals; D001273:Atmosphere Exposure Chambers; D004195:Disease Models, Animal; D000860:Hypoxia; D008297:Male; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D012756:Sheep; D014664:Vasodilation / Q000187:drug effects
D026902:Potassium Channel Blockers; D015761:4-Aminopyridine