Role of L-type Ca2+ channels, sarcoplasmic reticulum and Rho kinase in rat basilar artery contractile properties in a new model of subarachnoid hemorrhage

2015 ◽  
Vol 72 ◽  
pp. 64-72 ◽  
Author(s):  
Juan José Egea-Guerrero ◽  
Francisco Murillo-Cabezas ◽  
María Ángeles Muñoz-Sánchez ◽  
Angel Vilches-Arenas ◽  
Cristina Porras-González ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Sarcoplasmic Reticulum ◽  
Basilar Artery ◽  
Rho Kinase ◽  
Contractile Properties ◽  
New Model ◽  
Ca2 Channels

scholarly journals Alteration of Basilar Artery Rho-Kinase and Soluble Guanylyl Cyclase Protein Expression in a Rat Model of Cerebral Vasospasm following Subarachnoid Hemorrhage

2014 ◽  
Vol 2014 ◽  
pp. 1-8
Author(s):  
Chih-Jen Wang ◽  
Pei-Yu Lee ◽  
Bin-Nan Wu ◽  
Shu-Chuan Wu ◽  
Joon-Khim Loh ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Protein Kinase ◽  
Protein Expression ◽  
Cerebral Vasospasm ◽  
Basilar Artery ◽  
Guanylyl Cyclase ◽  
Autologous Blood ◽  
Rho Kinase ◽  
Soluble Guanylyl Cyclase ◽  
Western Blots

Background and Purpose. The vasoconstrictor endothelin-1 (ET-1) has been implicated in the pathogenesis of cerebral vasospasm following subarachnoid hemorrhage (SAH). Previous results showed that CGS 26303, an endothelin converting enzyme (ECE) inhibitor, effectively prevented and reversed arterial narrowing in animal models of SAH. In the present study, we assessed the effect of CGS 26303 on neurological deficits in SAH rats. The involvement of vasoactive pathways downstream of ET-1 signaling in SAH was also investigated.Methods. Sprague-Dawley rats were divided into five groups (n=6/group): (1) normal control, (2) SAH, (3) SAH+vehicle, (4) SAH+CGS 26303 (prevention), and (5) SAH+CGS 26303 (reversal). SAH was induced by injecting autologous blood into cisterna magna. CGS 26303 (10 mg/kg) was injected intravenously at 1 and 24 hr after the initiation of SAH in the prevention and reversal protocols, respectively. Behavioral changes were assessed at 48 hr after SAH. Protein expression was analyzed by Western blots.Results. Deficits in motor function were obvious in the SAH rats, and CGS 26303 significantly improved the rate of paraplegia. Expressions of rho-kinase-II and membrane-bound protein kinase C-δand rhoA were significantly increased, while those of soluble guanylyl cyclaseα1andβ1as well as protein kinase G were significantly decreased in the basilar artery of SAH rats. Treatment with CGS 26303 nearly normalized these effects.Conclusions. These results demonstrate that the rhoA/rho-kinase and sGC/cGMP/PKG pathways play pivotal roles in cerebral vasospasm after SAH. It also shows that ECE inhibition is an effective strategy for the treatment of this disease.

Role of local Ca2+ domains in activation of Ca(2+)-induced Ca2+ release in crayfish muscle fibers

1993 ◽  
Vol 264 (6) ◽  
pp. C1505-C1512 ◽  
Author(s):  
S. Gyorke ◽  
P. Palade
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cardiac Muscle ◽  
Binding Site ◽  
Equal Access ◽  
Crayfish Muscle ◽  
Simultaneous Measurements ◽  
Indicator Analysis ◽  
Dependent Processes ◽  
Ca2 Channels

Simultaneous measurements were made of crayfish muscle Ca2+ currents (ICa) and the intracellular Ca2+ transients they elicit due to Ca(2+)-induced Ca2+ release (CICR) from the sarcoplasmic reticulum (SR). Ca2+ concentration ([Ca2+]) elevations produced by Ca2+ entry via ICa were much more effective in triggering CICR than were ongoing release or homogeneous elevations of Ca2+ produced by photolysis of caged Ca2+. This suggests that [Ca2+] gradients exist when Ca2+ is elevated by ICa and that, during Ca2+ entry, [Ca2+] at the activation site of the release channels must be much greater than spatially averaged [Ca2+] reported by the indicator. Analysis of voltage dependencies of ICa inactivation and SR Ca2+ release suggest that both Ca(2+)-dependent processes are controlled by ICa via the nearest T tubule Ca2+ channel rather than by total ICa entry. The contribution of SR Ca2+ release to ICa inactivation studied with a two-pulse protocol was less than predicted if Ca2+ derived from SR Ca2+ release and from T tubule Ca2+ channels have equal access to the Ca2+ binding site controlling ICa inactivation. These results can be explained in terms of a scheme where sites for release activation and ICa inactivation are located in the same junctional gap subdomain, closer to the cytoplasmic mouth of the T tubule Ca2+ channel than to the cytoplasmic mouth of the SR Ca2+ release channels. Such a scheme could provide an explanation for the graded nature and selective control of CICR in this preparation as well as in vertebrate cardiac muscle.

Role of neuron density of the stellate ganglion on regulation of the basilar artery volume in subarachnoid hemorrhage: An experimental study

2011 ◽  
Vol 165 (2) ◽  
pp. 163-167 ◽  
Author(s):  
Selim Kayaci ◽  
Ayhan Kanat ◽  
Mehmet Dumlu Aydin ◽  
Ahmet Murat Musluman ◽  
Mete Eseoglu ◽  
...  
Keyword(s):  
Experimental Study ◽  
Subarachnoid Hemorrhage ◽  
Basilar Artery ◽  
Stellate Ganglion ◽  
Neuron Density

scholarly journals A Theory of the Mechanism of Cerebral Vasospasm and Its Reversal, the Role of Calcium and Cyclic AMP

1976 ◽  
Vol 3 (4) ◽  
pp. 223-226 ◽  
Author(s):  
Eric W. Peterson ◽  
Richard Leblanc
Keyword(s):  
Smooth Muscle ◽  
Subarachnoid Hemorrhage ◽  
Sarcoplasmic Reticulum ◽  
Cyclic Amp ◽  
Smooth Muscle Cell ◽  
Calcium Ion ◽  
Basic Mechanism ◽  
Free Intracellular Calcium ◽  
Intracellular Calcium Ion

SUMMARY:It is proposed that the basic mechanism of vasospasm which sometimes follows subarachnoid hemorrhage is dependent on increased free intracellular calcium ion produced by spasmogens from closely applied extravasated blood. Relaxation of this spasm occurs when the intracellular cyclic AMP levels are raised, resulting in sequestration of calcium ion by the vascular smooth muscle cell sarcoplasmic reticulum.

Upregulation of rho A and rho kinase messenger RNAs in the basilar artery of a rat model of subarachnoid hemorrhage

2000 ◽  
Vol 93 (3) ◽  
pp. 471-476 ◽  
Author(s):  
Yasushi Miyagi ◽  
Robin C. Carpenter ◽  
Toshinari Meguro ◽  
Andrew D. Parent ◽  
John H. Zhang
Keyword(s):  
Smooth Muscle ◽  
Subarachnoid Hemorrhage ◽  
Basilar Artery ◽  
Rho Kinase ◽  
Rt Pcr ◽  
Content Type ◽  
Blood Injection ◽  
Rho A ◽  
Rho Kinases ◽  
Fine Print

Object. Rho A, a small guanosine triphosphate—binding protein, and rho kinases have been suggested to play an important role in the agonist-induced myofilament Ca++ sensitization and cytoskeletal organization of smooth-muscle cells. To discover their possible roles in the prolonged contraction seen in cerebral vasospasm, the authors investigated the messenger (m)RNA expressions of rho A and rho-associated kinases α and β in the basilar artery (BA) of a rat double cisternal blood—injection model.Methods. An experimental subarachnoid hemorrhage (SAH) was achieved in rats by twice injecting autologous arterial blood into the cisterna magna of each animal. The mRNAs for rho A and rho-associated kinases α and β of the rat BA were analyzed using reverse transcription—polymerase chain reaction (RT-PCR). The cisternal blood injection induced a marked corrugation of elastic lamina and contraction of smooth-muscle cells observed with the aid of light and transmission electron microscopy in the rat BA on Days 3, 5, and 7. Results of the RT-PCR revealed that mRNAs for rho A and rho kinases α and β were expressed in the rat BA and that they were significantly upregulated and reached their peaks on Day 5.Conclusions. The mRNA upregulation of these proteins indicates that activation of rho A/rho kinase—related signal transduction pathways is involved in the development of long-lasting contraction of cerebral arteries after SAH.

Decreased endothelium-dependent relaxation in subarachnoid hemorrhage-induced vasospasm: role of ET-1

1995 ◽  
Vol 269 (3) ◽  
pp. H1009-H1015 ◽  
Author(s):  
M. Zuccarello ◽  
A. Romano ◽  
M. Passalacqua ◽  
R. M. Rapoport
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Receptor Antagonist ◽  
Basilar Artery ◽  
Arterial Blood ◽  
Eta Receptor ◽  
Eta Receptor Antagonist ◽  
Endothelium Dependent Relaxation

The purpose of this study was to test whether endothelium-dependent relaxation is decreased during acute vasospasm following subarachnoid hemorrhage (SAH) and the mechanism underlying the decrease. Basilar artery in situ was 35% constricted 3 days following injection of autologous arterial blood into the rabbit cisterna magna compared with vessels from control rabbits. In situ suffusion with the endothelium-dependent relaxant, acetylcholine (ACh; 10 microM), relaxed resting and serotonin (5-HT)-contracted control vessels but not vasospastic and 5-HT-contracted vasospastic vessels. In contrast, the relaxant potency and efficacy of ACh was similar in control and vasospastic vessels contracted with 5-HT in vitro. In situ suffusion with the ETA-receptor antagonist, BQ-123 (1 microM), reversed the vasospasm by 51% and restored the magnitude of ACh relaxation of vasospastic and 5-HT-contracted vasospastic vessels to that of controls. ACh in situ and in vitro relaxed endothelin-1 (ET-1)-contracted control vessels to a smaller magnitude than 5-HT-contracted control vessels. These results suggest, in contrast to previous studies, that endothelium-dependent relaxation is decreased during acute vasospasm following SAH. The decreased endothelium-dependent relaxation is secondary to the underlying ET-1-mediated spasm. The inhibition of endothelium-dependent relaxation observed in situ following SAH cannot be demonstrated in vitro, presumably due to loss of the ET-1-mediated vasospasm.

Brainstem hypoperfusion in severe symptomatic vasospasm following aneurysmal subarachnoid hemorrhage: role of basilar artery vasospasm

2006 ◽  
Vol 148 (9) ◽  
pp. 929-935 ◽  
Author(s):  
G. E. Sviri ◽  
G. W. Britz ◽  
D. H. Lewis ◽  
B. Ghodke ◽  
A. H. Mesiwala ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Basilar Artery ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Symptomatic Vasospasm

scholarly journals Role of Protein Kinase C in the Pathogenesis of Cerebral Vasospasm after Subarachnoid Hemorrhage

1993 ◽  
Vol 13 (2) ◽  
pp. 247-254 ◽  
Author(s):  
Masaharu Sako ◽  
Jun Nishihara ◽  
Shinsuke Ohta ◽  
Jinze Wang ◽  
Saburo Sakaki
Keyword(s):  
Protein Kinase C ◽  
Subarachnoid Hemorrhage ◽  
Protein Kinase ◽  
Cerebral Vasospasm ◽  
Basilar Artery ◽  
Sustained Contraction ◽  
Kinase C ◽  
Intracisternal Injection ◽  
Membrane Bound

This study investigated the role of protein kinase C (PKC) in the pathogenesis of vasospasm after experimental subarachnoid hemorrhage (SAH). PKC activation by intracisternal injection of a phorbol ester [12- O-tetradecanoylphorbol-13-acetate (TP)] induced dose-dependent, slowly developing, severe contraction of the basilar artery. A single intracisternal injection of TP (5 × 10−9 M in the CSF) induced sustained contraction lasting over 3 days, which almost paralleled the changes of membrane-bound PKC activity in the basilar arterial wall. In a two-hemorrhage SAH model, membrane-bound PKC activity in the basilar artery increased up to day 4 and returned to the control level by day 14, whereas angiographic contraction reached a maximum on day 7 and still persisted at a moderate level on day 14. Thus, there was a discrepancy between arterial PKC activity and arterial contraction. Multiple intracisternal injections of TP produced 30–40% sustained contraction of the basilar artery lasting for more than 10 days along with sustained activation of PKC to levels compatible with that observed in the SAH model. However, TP injection caused considerably milder histological changes in the basilar artery than those noted in the SAH model. We concluded that cerebral vasospasm after SAH cannot be explained solely on the basis of activation of the PKC pathway.

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