Contribution of potassium channels to active hyperemia of the canine diaphragm.
Glibenclamide, iberiotoxin, and apamin (blockers of ATP-sensitive, large-conductance, and small-conductance Ca(2+)-activated K+ channels, respectively) were infused into the diaphragmatic vasculature of anesthetized indomethacin-treated dogs to assess the contribution of K+ channels to active hyperemia. Diaphragmatic blood flow (Qphr) and O2 uptake (VO2di) were measured at rest and during 2 min of continuous left phrenic nerve stimulation at 0.5, 1, 2, and 4 Hz. These measurements were repeated before (control) and after the infusion of a selective K+ channel blocker in three groups of animals. Glibenclamide at 10(-5) M significantly attenuated Qphr at rest and in response to all stimulation frequencies. Whereas resting VO2di remained unchanged, glibenclamide infusion significantly reduced VO2di in response to all stimulation frequencies. The slope of the linear relationship between Qphr and VO2di, however, was not affected by glibenclamide. By comparison, infusion of iberiotoxin (10(-7) M) in a second group reduced Qphr at rest and in response to 0.5- and 1-Hz stimulation, whereas Qphr measured in response to 2- and 4-Hz stimulation remained similar to control values. Apamin (10(-6) M) infusion in a third group reduced only resting Qphr with no effect on active hyperemia during phrenic nerve stimulation. Neither iberiotoxin nor apamin influenced resting or stimulated VO2di. In all groups diaphragmatic tension measured after the infusion of K+ channel blockers remained similar to control values. These results indicate that K+ channels, especially those sensitive to glibenclamide, modulate the increase in Qphr and VO2di in response to moderate augmentation of metabolic demands.
Vanelli
G
G
Division of Critical Care, Royal Victoria Hospital, Montreal, Quebec, Canada.
Chang
H Y
HY
Gatensby
A G
AG
Hussain
S N
SN
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001784:Blood Gas Analysis; D003964:Diaphragm / Q000098:blood supply* / Q000378:metabolism; D004285:Dogs; D004558:Electric Stimulation; D005905:Glyburide / Q000494:pharmacology; D006940:Hyperemia / Q000503:physiopathology*; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D009119:Muscle Contraction / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology; D010791:Phrenic Nerve / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D014118:Toxins, Biological / Q000494:pharmacology
D007773:Lactates; D010455:Peptides; D015221:Potassium Channels; D014118:Toxins, Biological; D001030:Apamin; D019344:Lactic Acid; C064719:iberiotoxin; D005905:Glyburide; D015056:1-Methyl-3-isobutylxanthine