An ATP-sensitive potassium channel blocker decreases diaphragmatic circulation in anesthetized dogs

Abstract

The goal of this study was to determine whether in the dog ATP-sensitive K+ channels blocked with glibenclamide affect diaphragmatic blood flow [phrenic arterial blood flow (Qpa)] during both spontaneous breathing at rest and increased diaphragmatic activity. A control group (no glibenclamide; n = 4) and an experimental group (50 mg/kg of glibenclamide; n = 5) were studied. During spontaneous breathing at rest, Qpa was 15.0 ml.min-1 x 100 g-1 and decreased by 5% in the presence of glibenclamide. Diaphragmatic pacing (30 min-1) generated by phrenic nerve pacing produced an initial diaphragmatic tension-time index of 0.25 in both groups. A 50% decay in transdiaphragmatic pressure was reached at 165 s in the experimental group compared with 421 s in the control group. Diaphragmatic pacing increased Qpa by 46% in the experimental group and 65% in the control group, yielding a 63% greater vascular resistance in the experimental group. Phrenic vein K+ content at rest was unchanged by the presence of glibenclamide, being 3.6 +/- 0.16 mmol/l compared with 3.5 +/- 0.19 mmol/l in the control group. Phrenic nerve pacing in the control group produced a 13% increase in phrenic vein K+ content, whereas in the experimental group a 16% decrease was observed. We suggest that ATP-sensitive K+ channels play an important role in the modulation of Qpa.

Acute inhibition of ATP-sensitive K+ channels impairs skeletal muscle vascular control in rats during treadmill exercise

“…Specifically, the higher MAP and lower HR at rest with K ATP channel inhibition were coincident with large reductions in renal and splanchnic VC and suggest the occurrence of K ATP channel inhibition. This is in agreement with studies demonstrating a significant contribution of K ATP channels to basal vasomotor tone in the systemic circulation of conscious rats (18,28,36), hamsters (24,40), and dogs (11,48).…”

ATP-sensitive potassium channels mediate contraction-induced attenuation of sympathetic vasoconstriction in rat skeletal muscle.

“…In our experiments, glibenclamide also attenuated active hyperemia, which is consistent with previous studies in the canine diaphragm (35,36) and hamster cremaster muscle (37). We therefore considered the possibility that the attenuated active hyperemia may have contributed to the enhanced sympathetic vasoconstrictor response in the glibenclamide-treated animals.…”

Effects of inhibition of ATP-sensitive potassium channels on metabolic vasodilation in the human forearm

“…Our observations in skeletal muscle are not in keeping with previous data from some animal studies [22,23,[26][27][28], but they are consistent with the findings from the only published study to date undertaken in conscious mammals [18]. Apart from species-related and other methodological differences, additional factors may account for the aforementioned differences.…”

“…A body of experimental evidence suggests that K ATP channels are involved in regulating skeletal muscle blood flow during the increase in muscle metabolism associated with exercise [22,23,[26][27][28]. However, recent experiments in conscious pigs do not provide support for these findings [18].…”