Korean J Anesthesiol.  2003 Dec;45(6):754-761. 10.4097/kjae.2003.45.6.754.

Effects of Pinacidil, Tetrathylammonium and Glibenclamide on Hypoxic Vasoconstriction in Isolated Perfused Rabbit Lungs

• Ro YJ
• Yun WH
• Kim CS
• Min SW
• Kim SD
• Kim YL

• KMID: 2039744
• DOI: http://doi.org/10.4097/kjae.2003.45.6.754

Abstract

BACKGROUND: This study investigated the effects of the K+ channel opener, pinacidil on hypoxic pulmonary vasoconstriction in isolated perfused rabbit lungs. In order to evaluate the vasodilatation mechanism of K+ channel opener, we also studied the effects of two K+ channel blocker, tetraethylammonium (TEA), a Ca2+ activated K+ channel blocker and glibenclamide (GLB), an ATP-sensitive K+ channel blocker.
METHODS
Isolated lungs from white rabbits were ventilated with a normoxic gas (21%O2-5%CO2-74%N2) and a hypoxic gas (3%O2- 5%CO2-92%N2) alternatively, and then perfused with blood-containing perfusate solution. After a hypoxic pressor response (HPR) had been obtained, various drugs were added to the perfusate reservoir to achieve the predetermined circulating concentration, and the influences of the drugs on HPR were then tested.
RESULTS
Pinacidil (0.3-6.0 mcM) produced a dose-dependent pulmonary vasodilation on hypoxic ventilation challenge. TEA (1 mM) caused pulmonary vasoconstriction in normoxic ventilation and potentiated a hypoxic pressor response. When the hypoxic pressor response was potentiated by TEA, pinacidil (1.0, 3.0 mcM) reduced the contraction, but GLB did not cause pulmonary vasoconstriction under normoxic ventilation, potentiate a hypoxic pressor response.
CONCLUSIONS
Piacidil is capable of opposing the pulmonary responses of acute hypoxia. Moreover the effects of TEA and GLB suggest that HPV might be mediated through Ca2+ activated K+ channels, not through ATP-sensitive K+ channels.

Keyword

hypoxic pulmonary vasoconstriction; isolated perfused rabbit lungs; potassium channel blocker; potassium channel opener

MeSH Terms

Anoxia
Glyburide*
Lung*
Pinacidil*
Potassium Channels, Calcium-Activated
Rabbits
Tea
Tetraethylammonium
Vasoconstriction*
Vasodilation
Ventilation
Glyburide
Pinacidil
Potassium Channels, Calcium-Activated
Tea
Tetraethylammonium