From the Department of Anesthesiology, Baylor College of Medicine,
Houston, Tex.
Correspondence to Robert M. Bryan, Jr, PhD, Department of Anesthesiology, Room 434D, Baylor College of Medicine, Houston, TX 77030. E-mail rbryan{at}bcm.tmc.edu
Background and PurposeSeveral
recent studies have demonstrated that inward rectifier potassium
channels (Kirs) are located on vascular smooth muscle of
cerebral arteries in the rat. Activation of the Kirs
dilates the arteries by relaxing the vascular smooth muscle. We tested
the following hypothesis in the present study: function of inward
rectifier potassium channels is altered after
ischemia/reperfusion (I/R).
MethodsTemporary (2-hour) focal ischemia was induced in
male Long-Evans rats (3% isoflurane anesthesia) by the
intraluminal filament model. After 24 hours of reperfusion, ipsilateral
and contralateral middle cerebral arteries (MCAs) were harvested and
mounted on micropipettes, pressurized to 85 mm Hg, and luminally
perfused.
ResultsResting diameters for contralateral (control) and
ipsilateral (I/R) MCAs were not significantly different (215±4
µm and 211±5 µm [n=6 and n=7], respectively). Activation of
the Kirs by abluminal administration of 15 mmol/L KCl
to the control MCAs dilated the MCA by 34±4% (n=8). Activation of the
Kirs in I/R MCAs produced a dilation of only 11±3% (n=8;
P<0.001 compared with control). BaCl2
(75 µmol/L), a concentration-selective inhibitor of
the Kirs, significantly attenuated the dilation produced by
15 mmol/L KCl in control MCAs but not in the I/R MCAs.
Endothelial-mediated dilations elicited by the luminal
administration of uridine triphosphate (10 µmol/L) produced
similar dilations in both groups (32±5% for sham [n=4] and 33±2%
for I/R [n=4]), indicating that dilator function in general was not
altered in I/R vessels.
ConclusionsWe conclude that Kir function is altered
after I/R. The Kir altered function is likely to exacerbate
the brain injury occurring after I/R.
Department
of Physiology and Pharmacology Wake Forest University
School of Medicine Winston-Salem, North Carolina
© 1998 American Heart Association, Inc.
Original Contributions
Altered Function of Inward Rectifier Potassium Channels in Cerebrovascular Smooth Muscle After Ischemia/Reperfusion
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