The gap junction is important in the propagation of dilation/constriction signals along vessels for coordinated behavior in control of vascular tone. The authors hypothesized that gap junctions might play a role in cerebral vasospasm following subarachnoid hemorrhage (SAH). The aims of the present study were to investigate the role of gap junctions and to observe the potential therapeutic efficacy of gap junction blockers in cerebral vasospasm in vitro and in vivo.
开云体育世界杯赔率
For the in vitro investigation, the effect of heptanol on the oxyhemoglobin (HbO2)-induced contraction of isolated rabbit basilar arteries (BAs) was observed by using an isometric tension-recording method. For the in vivo experiments, the potential therapeutic efficacy of heptanol and carbenoxolone was surveyed after it was given intravenously in the rabbit double-hemorrhage model. Light microscopy was performed to assess the morphological changes in the arteries examined.
Results
For the in vitro method, heptanol significantly inhibited the sustained contraction induced both by HbO2and K+in the BA rings. The magnitude of the heptanol-induced relaxation was dose dependent. The inhibitory effect of heptanol on the K+-induced vasoconstriction was weaker than that on the HbO2-induced constriction. After arterial rings were pretreated for 10 minutes, heptanol significantly decreased their responses to the HbO2-induced contraction. For the in vivo method, heptanol and carbenoxolone significantly decreased the narrowing of BAs when given intravenously in the rabbit double-hemorrhage model. In both treated groups, the diameters of the arteries had not changed significantly on Day 7 compared with those of the arteries in the SAH + vehicle and the SAH-only group.
Conclusions
庚醇、生胃酮显著抑制the experimental cerebral vasospasm both in vitro and in vivo. Blockage of gap junctions is a probable candidate for a new approach in the treatment of cerebral vasospasm. Gap junctions may play a pathophysiological role in cerebral vasospasm.
Abbreviations used in this paper:
BA = basilar artery;HbO2 = oxyhemoglobin;SAH = subarachnoid hemorrhage;SEM = standard error of the mean.
Address correspondence to:Tao Hong, M.D., Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China. email:ht2000@vip.sina.com.
Alvarez-Maubecin
V
,
García-Hernández
F
,
Williams
JT
,
Van Bockstaele
EJ
:
Functional coupling between neurons and glia
.J Neurosci
20
:
4091
- - - - - -
4098
,
2000
10.1523/JNEUROSCI.20-11-04091.2000)| false
ChristGJ:Modulation of alpha 1-adrenergic contractility in isolated vascular tissues by heptanol: a functional demonstration of the potential importance of intercellular communication to vascular response generation.生命科学56:709- - - - - -721,1995
Christ
GJ
:
Modulation of alpha 1-adrenergic contractility in isolated vascular tissues by heptanol: a functional demonstration of the potential importance of intercellular communication to vascular response generation
.生命科学
56
:
709
- - - - - -
721
,
1995
10.1016/0024-3205(95)00001-M)| false
ChristGJ,&BrinkPR:Analysis of the presence and physiological relevance of subconducting states of connexin43-derived gap junction channels in cultured human corporal vascular smooth muscle cells.Circ Res84:797- - - - - -803,1999
Christ
GJ
,
Brink
PR
:
Analysis of the presence and physiological relevance of subconducting states of connexin43-derived gap junction channels in cultured human corporal vascular smooth muscle cells
.Circ Res
84
:
797
- - - - - -
803
,
1999
10.1161/01.RES.84.7.797)| false
ChristGJ,&BrinkPR:Gap junctions in isolated rat aorta: evidence for contractile responses that exhibit a differential dependence on intercellular communication.Braz J Med Biol Res33:423- - - - - -429,2000
Christ
GJ
,
Brink
PR
:
Gap junctions in isolated rat aorta: evidence for contractile responses that exhibit a differential dependence on intercellular communication
.Braz J Med Biol Res
33
:
423
- - - - - -
429
,
2000
10.1590/S0100-879X2000000400008)| false
ChristGJ,,MorenoAP,,ParkerME,,GondreCM,,ValcicM,&MelmanA,et al.:Intercellular communication through gap junctions: a potential role in pharmacomechanical coupling and syncytial tissue contraction in vascular smooth muscle isolated from the human corpus cavernosum.生命科学49:195- - - - - -200,1991
Christ
GJ
,
Moreno
AP
,
Parker
ME
,
Gondre
CM
,
Valcic
M
,
Melman
A
,
:
Intercellular communication through gap junctions: a potential role in pharmacomechanical coupling and syncytial tissue contraction in vascular smooth muscle isolated from the human corpus cavernosum
.生命科学
49
:
195
- - - - - -
200
,
1991)| false
ChristGJ,,SpektorM,,BrinkPR,&BarrL:Further evidence for the selective disruption of intercellular communication by heptanol.Am J Physiol276:H1911- - - - - -H1917,1999
Christ
GJ
,
Spektor
M
,
Brink
PR
,
Barr
L
:
Further evidence for the selective disruption of intercellular communication by heptanol
.Am J Physiol
276
:
H1911
- - - - - -
H1917
,
1999)| false
ChristGJ,,SprayDC,,el-SabbanM,,MooreLK,&BrinkPR:Gap junctions in vascular tissues. Evaluating the role of intercellular communication in the modulation of vasomotor tone.Circ Res79:631- - - - - -646,1996
Christ
GJ
,
Spray
DC
,
el-Sabban
M
,
Moore
LK
,
Brink
PR
:
Gap junctions in vascular tissues. Evaluating the role of intercellular communication in the modulation of vasomotor tone
.Circ Res
79
:
631
- - - - - -
646
,
1996
10.1161/01.RES.79.4.631)| false
De WitC,,WolfleSE,&HopflB:Connexin-dependent communication within the vascular wall: contribution to the control of arteriolar diameter.Adv Cardiol42:268- - - - - -283,2006
De Wit
C
,
Wolfle
SE
,
Hopfl
B
:
Connexin-dependent communication within the vascular wall: contribution to the control of arteriolar diameter
.Adv Cardiol
42
:
268
- - - - - -
283
,
2006)| false
GioiaAE,,WhiteRP,,BakhtianB,&RobertsonJT:Evaluation of the efficacy of intrathecal nimodipine in canine models of chronic cerebral vasospasm.J Neurosurg62:721- - - - - -728,1985
Gioia
AE
,
White
RP
,
Bakhtian
B
,
Robertson
JT
:
Evaluation of the efficacy of intrathecal nimodipine in canine models of chronic cerebral vasospasm
.J Neurosurg
62
:
721
- - - - - -
728
,
1985
10.3171/jns.1985.62.5.0721)| false
HillCE,,RummeryN,,HickeyH,&SandowSL:Heterogeneity in the distribution of vascular gap junctions and connexins: implications for function.Clin Exp Pharmacol Physiol29:620- - - - - -625,2002
Hill
CE
,
Rummery
N
,
Hickey
H
,
Sandow
SL
:
Heterogeneity in the distribution of vascular gap junctions and connexins: implications for function
.Clin Exp Pharmacol Physiol
29
:
620
- - - - - -
625
,
2002
10.1046/j.1440-1681.2002.03699.x)| false
HillsCE,,BlandR,,WheelansDC,,BennettJ,,RoncoPM,&SquiresPE:Glucose-evoked alterations in connexin43-mediated cell-to-cell communication in human collecting duct: a possible role in diabetic nephropathy.Am J Physiol Renal Physiol291:F1045- - - - - -F1051,2006
Hills
CE
,
Bland
R
,
Wheelans
DC
,
Bennett
J
,
Ronco
PM
,
Squires
PE
:
Glucose-evoked alterations in connexin43-mediated cell-to-cell communication in human collecting duct: a possible role in diabetic nephropathy
.Am J Physiol Renal Physiol
291
:
F1045
- - - - - -
F1051
,
2006
10.1152/ajprenal.00344.2005)| false
Hong
T
,
Hill
CE
:
Restricted expression of the gap junctional connexin 43 in the arterial system of the rat
.J Anat
192
:
583
- - - - - -
593
,
1998
10.1046/j.1469-7580.1998.19240583.x)| false
Kamermans
M
,
Fahrenfort
I
,
Janssen-Bienhold
U
,
Schultz
K
,
Sjoerdsma
T
,
Wieler
R
:
Hemichannel mediated inhibition in the outer retina
.Science
292
:
1178
- - - - - -
1180
,
2001
10.1126/science.1060101)| false
Kuwayama
A
,
Zervas
NT
,
Belson
R
,
Shintani
A
,
Pickren
K
:
A model for experimental cerebral arterial spasm
.Stroke
3
:
49
- - - - - -
56
,
1972
10.1161/01.STR.3.1.49)| false
LeeRM,,GarfieldRE,,ForrestJB,&DanielEE:Morphometric study of structural changes in the mesenteric blood vessels of spontaneously hypertensive rats.Blood Vessels20:57- - - - - -71,1983
Lee
RM
,
Garfield
RE
,
Forrest
JB
,
Daniel
EE
:
Morphometric study of structural changes in the mesenteric blood vessels of spontaneously hypertensive rats
.Blood Vessels
20
:
57
- - - - - -
71
,
1983)| false
Li
X
,
Simard
JM
:
Multiple connexins form gap junction channels in rat basilar artery smooth muscle cells
.Circ Res
84
:
1277
- - - - - -
1284
,
1999
10.1161/01.RES.84.11.1277)| false
MartinW,,VillaniGM,,JothianandanD,&FurchgottRF:Selective blockade of endothelium-dependent and glyceryl trinitrate-induced relaxation by hemoglobin and by methylene blue in the rabbit aorta.J Pharmacol Exp Ther232:708- - - - - -716,1985
Martin
W
,
Villani
GM
,
Jothianandan
D
,
Furchgott
RF
:
Selective blockade of endothelium-dependent and glyceryl trinitrate-induced relaxation by hemoglobin and by methylene blue in the rabbit aorta
.J Pharmacol Exp Ther
232
:
708
- - - - - -
716
,
1985)| false
Oviedo-Orta
E
,
Howard
EW
:
Gap junctions and connexin-mediated communication in the immune system
.Biochim Biophys Acta
1662
:
102
- - - - - -
112
,
2004
10.1016/j.bbamem.2003.10.021)| false
RudisuliA,&WeingartR:Electrical properties of gap junction channels in guinea pig ventricular cell pairs revealed by exposure to heptanol.Pflugers Arch415:12- - - - - -21,1989
SaezJC,,ConnorJA,,SprayDC,&BennettMV:Hepatocyte gap junctions are permeable to the second messenger, inositol 1,4,5-trisphosphate, and to calcium ions.Proc Natl Acad Sci U S A86:2708- - - - - -2712,1989
Saez
JC
,
Connor
JA
,
Spray
DC
,
Bennett
MV
:
Hepatocyte gap junctions are permeable to the second messenger, inositol 1,4,5-trisphosphate, and to calcium ions
.Proc Natl Acad Sci U S A
86
:
2708
- - - - - -
2712
,
1989
10.1073/pnas.86.8.2708)| false
Shishido
T
,
Suzuki
R
,
Qian
L
,
Hirakawa
K
:
The role of superoxide anions in the pathogenesis of cerebral vasospasm
.Stroke
25
:
864
- - - - - -
868
,
1994
10.1161/01.STR.25.4.864)| false
VancheriC,,MastruzzoC,,TomaselliV,,SortinoMA,,D'AmicoL,&BellistriG,et al.:Normal human lung fibroblasts differently modulate interleukin-10 and interleukin-12 production by monocytes: implications for an altered immune response in pulmonary chronic inflammation.Am J Respir Cell Mol Biol25:592- - - - - -599,2001
Vancheri
C
,
Mastruzzo
C
,
Tomaselli
V
,
Sortino
MA
,
D'Amico
L
,
Bellistri
G
,
:
Normal human lung fibroblasts differently modulate interleukin-10 and interleukin-12 production by monocytes: implications for an altered immune response in pulmonary chronic inflammation
.Am J Respir Cell Mol Biol
25
:
592
- - - - - -
599
,
2001
10.1165/ajrcmb.25.5.4609)| false
WhiteRP,&RobertsonJT:Role of plasmin, thrombin, and anti-thrombin as etiological factors in delayed cerebral vasospasm.开云体育app官方网站下载入口16:27- - - - - -35,1985
White
RP
,
Robertson
JT
:
Role of plasmin, thrombin, and anti-thrombin as etiological factors in delayed cerebral vasospasm
.开云体育app官方网站下载入口
16
:
27
- - - - - -
35
,
1985)| false
YamamotoY,,KlemmMF,,EdwardsFR,&SuzukiH:Intercellular electrical communication among smooth muscle and endothelial cells in guinea-pig mesenteric arterioles.J Physiol535:181- - - - - -195,2001
