EFFECTS OF POTASSIUM CHANNEL BLOCKERS ON BASAL VASCULAR TONE AND REACTIVE HYPEREMIA OF CANINE DIAPHRAGM

Glibenclamide, iberiotoxin, and apamin (blockers of ATP-sensitive, lar ge-conductance, and small-conductance Ca2+-activated potassium channel s, respectively) were infused into the diaphragmatic vasculature of an esthetized dogs to assess the contribution of these channels in the re gulation of basal tone and the response to brief occlusions of the lef t phrenic artery (reactive hyperemia). Baseline phrenic flow (Q(phr)), peak postocclusive flow, and reactive hyperemia duration in response to 10-, 30-, 60-, and 120-s arterial occlusions were measured before ( control) and after the infusion of K+ channel blockers in three groups of animals. Glibenclamide at 5 x 10(-6), 1 x 10(-5), and 8 x 10(-5) M increased baseline phrenic resistance to 140, 204, and 192% of contro l values, respectively. Peak postocclusive Q(phr) and duration of hype remia in response to all occlusion durations were significantly attenu ated after glibenclamide infusion. Iberiotoxin infusion at 1 x 10(-8), 3 x 10(-8), and 1 x 10(-7) M increased phrenic resistance to 141, 133 , and 146% of control values, respectively. By comparison, baseline ph renic resistance rose to 159 and 145% of control in response to 1 x 10 (-7) and 1 x 10(-6) M apamin, respectively. Iberiotoxin and apamin red uced peak postocclusive flow and duration of hyperemia only in respons e to 10- and 30-s occlusions. We infused K+ channel blockers along wit h lemakalim into the diaphragm during constant flow perfusion in separ ate groups of animals. When infused alone, lemakalim reduced phrenic r esistance by 60-70%. Glibenclamide dose dependently reversed lemakalim -induced vasodilation, whereas neither iberiotoxin nor apamin influenc ed this dilation. These results suggest that baseline resistance and r eactive hyperemia of the diaphragm are regulated in part by the activi ties of potassium channels, particularly those sensitive to glibenclam ide.