Brain Research 880 2000 159–166 www.elsevier.com locate bres
Research report
The effects of potassium on the rat middle cerebral artery
E.M. Golding , M.L. Steenberg, T.D. Johnson, R.M. Bryan Jr
Department of Anesthesiology , Baylor College of Medicine, Houston, TX 77030, USA
Accepted 2 August 2000
Abstract
1 1
After traumatic brain injury, extracellular K in brain can dramatically increase. We studied the effects of increased K
on the isolated pressurized rat middle cerebral artery MCA. MCAs 200–250 mm OD were isolated, cannulated with glass micropipettes, and
1 1
1
pressurized. K was increased in the extraluminal bath using three paradigms: 1 isotonic K
K where increases in K
were offset
iso 1
1 1
1
by decreases in Na , 2 hypertonic K K
where K was increased without a concomitant adjustment of Na , and 3 K
, a
hyper suc
1
solution using K but with the addition of sucrose to obtain a hypertonic solution. Increases in K
in the extraluminal bath produced
iso 1
significant dilations approximately 20 at 21 mM K in all three groups K
, K , and K
. With the K and K
groups, the
iso hyper
suc hyper
suc 1
25
magnitude of the dilation diminished with further increases in K .
L
-NAME 10 M, an inhibitor of nitric oxide synthase, had no effect
1
on the response of the K and K
groups at 21 mM but significantly enhanced constrictions of the MCAs above 40 mM K
hyper suc
1
compared to the control. The K group was not affected by
L
-NAME at any K concentration and showed profound constrictions above
iso 1
1
40 mM K . We conclude that changes in the K concentration and osmolality of the extracellular fluid may have profound effects on the
cerebral vasculature.
2000 Elsevier Science B.V. All rights reserved.
Theme : Disorders of the nervous system
Topic : Trauma
1
Keywords : Cerebral arteries; Inward rectifier K
channels; Nitric oxide; Osmolality
1
1. Introduction Although the effects of increased K
on vascular smooth
muscle have
been extensively
studied
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Extracellular K , which is normally 3–5 mM, increases [4,14,15,21,25,30,37,41,43,44], newly acquired informa-
to 10–12 mM when neurons are activated [39]. The tion warrants a re-evaluation of this relationship between
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increased K at the vessel wall activates inward rectifier K
K and vascular cells smooth muscle and endothelium. It
channels K s, hyperpolarizes the vascular smooth mus- has become apparent over the last 20 years that the
ir
cle, and
dilates cerebral
arteries arterioles endothelium can release factors which constrict or relax
[4,18,21,22,25,28–30,36]. the vascular smooth muscle [12]. The direct and indirect
1
During pathological conditions, such as stroke and effects of increased K
on the endothelium were either not
1
traumatic brain injury TBI, extracellular K can increase
known at the time and or were not taken into considera- to 50–80 mM in brain [1,13,16,19,33,39,40]. The extracel-
tion when interpreting the results of the above-mentioned
1
lular K concentration may normalize several minutes
experiments. This issue becomes very significant in light after injury or remain elevated in excess of 30 min when
of recent reports showing that vascular smooth muscle can the injury involves cortical contusion [40]. At these higher
influence endothelium through myo-endothelial junctions
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concentrations, K no longer hyperpolarizes and dilates
gap junctions [9]. Increases in Ca in the vascular
1
cerebral vessels. Instead, it depolarizes the vascular smooth smooth muscle which occur with extracellular K
con- muscle and constricts [14,44].
centrations above 20–30 mM can be transmitted to the endothelium via the myoendothelial junctions [9]. In-
21
creased Ca in the endothelium may stimulate the release
Corresponding author. Tel.: 11-713-798-7720; fax: 11-713-798-
of NO and possibly other relaxing factors [11,12]. Thus,
7644. E-mail address
: egoldingbcm.tmc.edu E.M. Golding.
the release of endothelial factors during conditions of
0006-8993 00 – see front matter
2000 Elsevier Science B.V. All rights reserved. P I I : S 0 0 0 6 - 8 9 9 3 0 0 0 2 7 9 3 - 1
160 E
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increased K for instance stroke and TBI could influence
measure of perfusion pressure. A flow meter [11, Gil-
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the overall response to K . mont Instruments, Barrington, IL, USA, connected to the
The purpose of this investigation was to study the tubing leading to the output reservoir, measured luminal
1
effects of changes in the concentration of extracellular K flow [5]. The luminal perfusate was gassed in the input
on the contractile state of the rat middle cerebral artery. reservoir. In addition, the luminal perfusate traveled
Specifically we tested two hypotheses: first, the constric- through gas permeable silastic tubing in the bath prior to
1
tion produced by increased extracellular K 30–80 mM
perfusing the lumen of each artery to ensure that it was as occurs following TBI in the rat middle cerebral artery
properly gassed and equilibrated to 378C. Samples of PSS MCA is attenuated by the stimulated production of NO in
from the bath and luminal perfusate were analyzed for endothelium and second, that increases in osmolality that
pO , pCO , and pH using a Corning model 280 analyzer
2 2
are observed after TBI [20,45], are responsible for the NO Medfield, MA, USA.
component. The vessels were magnified using an inverted micro-
scope equipped with a video camera and monitor. Outside diameters of the arteries were measured directly from the
video screen.
2. Materials and methods
