Role of potassium channels in isoflurane- and sevoflurane-induced attenuation of hypoxic pulmonary vasoconstriction in isolated perfused rabbit lungs

Background: Although potassium channels are thought to be responsible for t he initiation of hypoxic pulmonary vasoconstriction (HPV), their role in th e HPV-inhibitory effect of volatile anesthetics is unclear. The current stu dy tested if the HPV-inhibitory effect of isoflurane and sevoflurane can be affected by changing the potassium-channel opening status with specific po tassium-channel inhibitors in Isolated rabbit lungs. Methods. isolated rabbit lungs were divided into eight groups (n = 6 each i n isoflurane groups and n = 8 in sevoflurane groups): those receiving no In hibitor treatment = control-isoflurane and control-sevoflurane groups; thos e treated with an adenosine triphosphate-sensitive potassium (K-ATP)-channe l inhibitor, glibenclamide = glibenclamide-isoflurane and glibenciamide-sev oflurane groups; those treated with a high-conductance calcium-activated po tassium (K-Ca)-channel Inhibitor, iberiotoxin = iberiotoxin-isoflurane and iberiotoxin-sevoflurane groups; and those treated with a voltage-sensitive potassium (K-V)-channel Inhibitor, 4-aminopyridine = 4-aminopyridine-isoflu rane and 4-aininopyridine-sevoflurane groups. The effect of anesthetic on H PV was tested by exposure of the lungs to isoflurane at a concentration of 0, 0.5, 1, or 2 minimum alveolar concentration, or to sevoflurane at a conc entration of 0, 0.5, 1, or 1.62 minimum alveolar concentration. The relatio n between anesthetic concentrations and the HPV response was analyzed by th e Wagner equation. Results: The inhibition of K-V channels by 4-aminopyridine and K-Ca channel s by Iberiotoxin augmented the HPV response. The isoflurane-induced attenua tion of HPV was attenuated by voltage-sensitive potassium-channel inhibitio n with 4-aminopyridine, potentiated by K-Ca-channel inhibition with iberiot oxin, but not affected by K-ATP-channel inhibition with glibenclamide. The sevoflurane-induced attenuation of HPV was not affected by any of the potas sluim-channel inhibitors. Conclusions: Isoflurane may modulate the HPV response partially through K-C a and K-V channels, but sevoflurane may attenuate the HPV response through other pathways rather than through the currently investigated potassium cha nnels in isolated rabbit lungs.