scholarly journals Upregulation of Relaxin after Experimental Subarachnoid Hemorrhage in Rabbits

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Yuichiro Kikkawa ◽  
Satoshi Matsuo ◽  
Ryota Kurogi ◽  
Akira Nakamizo ◽  
Masahiro Mizoguchi ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Vasospasm ◽  
Basilar Artery ◽  
Messenger Rna ◽  
Cerebral Arteries ◽  
Enzyme Linked Immunosorbent Assay ◽  
Endothelin 1 ◽  
Basilar Arteries ◽  
Experimental Subarachnoid Hemorrhage

Background. Although relaxin causes vasodilatation in systemic arteries, little is known about its role in cerebral arteries. We investigated the expression and role of relaxin in basilar arteries after subarachnoid hemorrhage (SAH) in rabbits.Methods. Microarray analysis with rabbit basilar artery RNA was performed. Messenger RNA expression of relaxin-1 and relaxin/insulin-like family peptide receptor 1 (RXFP1) was investigated with quantitative RT-PCR. RXFP1 expression in the basilar artery was investigated with immunohistochemistry. Relaxin concentrations in cerebrospinal fluid (CSF) and serum were investigated with an enzyme-linked immunosorbent assay. Using human brain vascular smooth muscle cells (HBVSMC) preincubated with relaxin, myosin light chain phosphorylation (MLC) was investigated with immunoblotting after endothelin-1 stimulation.Results. After SAH, RXFP1 mRNA and protein were significantly downregulated on day 3, whereas relaxin-1 mRNA was significantly upregulated on day 7. The relaxin concentration in CSF was significantly elevated on days 5 and 7. Pretreatment with relaxin reduced sustained MLC phosphorylation induced by endothelin-1 in HBVSMC.Conclusion. Upregulation of relaxin and downregulation of RXFP1 after SAH may participate in development of cerebral vasospasm. Downregulation of RXFP1 may induce a functional decrease in relaxin activity during vasospasm. Understanding the role of relaxin may provide further insight into the mechanisms of cerebral vasospasm.

scholarly journals Role of p53 and Apoptosis in Cerebral Vasospasm after Experimental Subarachnoid Hemorrhage

2005 ◽  
Vol 25 (5) ◽  
pp. 572-582 ◽  
Author(s):  
Changman Zhou ◽  
Mitsuo Yamaguchi ◽  
Austin RT Colohan ◽  
John H Zhang
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Vasospasm ◽  
Cerebral Arteries ◽  
Tunel Staining ◽  
Positive Staining ◽  
Key Factor ◽  
Basilar Arteries ◽  
Experimental Subarachnoid Hemorrhage

Our previous studies indicate that apoptosis in endothelial cells of major cerebral arteries contributes to cerebral vasospasm after subarachnoid hemorrhage (SAH). This study examined the pathologic roles of tumor suppressor p-53 in cerebral vasospasm using an established dog double-hemorrhage model. Twenty mongrel dogs were divided into four groups: (1) control, (2) SAH, (3) SAH+DMSO (vehicle), and (4) SAH+pifithrin-α (PFT) (p53 inhibitor). The p53 inhibitor (200 nmol/L) was injected into the cisterna magna daily from Day 0 through Day 3. Angiogram was performed on Day 0 and Day 7. Western blot, cell proliferation assay, histology, and TUNEL staining were conducted on the basilar arteries collected on Day 7 after SAH. The arterial diameter on Day 7 was 42%±4%, 40%±5%, and 59%±4% for SAH, SAH+DMSO, and SAH+PFT, respectively. In addition, positive staining of TUNEL and increased protein expression of p53, Bax, and PCNA in the basilar artery were observed on Day 7. PFT suppressed apoptosis in endothelial cells and proliferation in smooth muscle cells, and attenuated angiographic vasospasm. In conclusion, p53 may be a key factor in endothelial apoptosis and smooth muscle proliferation after SAH. Inhibition of p53 may potentially reduce or even prevent cerebral vasospasm.

scholarly journals Subarachnoid Hemorrhage and the Role of Potassium Channels in Relaxations of Canine Basilar Artery to Nitrovasodilators

1998 ◽  
Vol 18 (2) ◽  
pp. 186-195 ◽  
Author(s):  
Hisashi Onoue ◽  
Zvonimir S. Katusic
Keyword(s):  
Nitric Oxide ◽  
Subarachnoid Hemorrhage ◽  
Sodium Nitroprusside ◽  
Basilar Artery ◽  
Cyclic Gmp ◽  
Cerebral Arteries ◽  
Basilar Arteries ◽  
Canine Basilar Artery ◽  
Gmp Production

This study was designed to determine the effect of subarachnoid hemorrhage (SAH) on potassium (K+) channels involved in relaxations of cerebral arteries to nitrovasodilators. The effects of K+ channel inhibitors on relaxations to 3-morpholinosydnonimine (SIN-1) and sodium nitroprusside (SNP) were studied in rings of basilar arteries obtained from untreated dogs and dogs exposed to SAH. The levels of cyclic GMP were measured by radioimmunoassay. In rings without endothelium, concentration-dependent relaxations to SIN-1 (10−9 − 10−4 mol/L) and SNP (10−9 − 10−4 mol/L) were not affected by SAH, whereas increase in cyclic GMP production stimulated by SIN-1 (10−6 mol/L) was significantly suppressed after SAH. The relaxations to SIN-1 and SNP were reduced by charybdotoxin (CTX; 10−7 mol/L), a selective Ca2+-activated K+ channel inhibitor, in both normal and SAH arteries; however, the reduction of relaxations by CTX was significantly greater in SAH arteries. By contrast, the relaxations to these nitrovasodilators were not affected by glyburide (10−5 mol/L), an ATP-sensitive K+ channel inhibitor, in both normal and SAH arteries. These findings suggest that in cerebral arteries exposed to SAH, Ca2+-activated K+ channels may play a compensatory role in mediation of relaxations to nitric oxide. This may help to explain mechanisms of relaxations to nitrovasodilators in arteries with impaired production of cyclic GMP.

Potential role of JAK2 in cerebral vasospasm after experimental subarachnoid hemorrhage

2008 ◽  
Vol 1214 ◽  
pp. 136-144 ◽  
Author(s):  
Gang Chen ◽  
Jiang Wu ◽  
Caixia Sun ◽  
Meng Qi ◽  
Chunhua Hang ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Vasospasm ◽  
Potential Role ◽  
Experimental Subarachnoid Hemorrhage

Role of Cyclooxygenase-2 in Relation to Nitric Oxide and Endothelin-1 on Pathogenesis of Cerebral Vasospasm After Subarachnoid Hemorrhage in Rabbit

2016 ◽  
Vol 7 (3) ◽  
pp. 220-227 ◽  
Author(s):  
Akira Munakata ◽  
Masato Naraoka ◽  
Takeshi Katagai ◽  
Norihito Shimamura ◽  
Hiroki Ohkuma
Keyword(s):  
Nitric Oxide ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Vasospasm ◽  
Cyclooxygenase 2 ◽  
Endothelin 1

Cerebral vasospasm: contractile activity of hemoglobin in isolated canine basilar arteries

1980 ◽  
Vol 53 (6) ◽  
pp. 787-793 ◽  
Author(s):  
Takeo Tanishima
Keyword(s):  
Cerebral Vasospasm ◽  
Basilar Artery ◽  
Contractile Activity ◽  
Cerebral Arteries ◽  
Adenosine Monophosphate ◽  
Active Species ◽  
Exchange Chromatography ◽  
Basilar Arteries ◽  
Chronic Cerebral Vasospasm

✓ Recent studies suggest the possible role of the red blood cell (RBC) in causing chronic cerebral vasospasm. However, the basic action of hemoglobin (Hb), the major component of the RBC, on cerebral arteries remains unknown. The present study was undertaken to analyze the contractile effects of human Hb (purified by ion-exchange chromatography) on canine arteries in vitro. The contractile activity of lysed RBC was shown to be derived from Hb. Hemoglobin in oxygenated form (oxyHb) caused a maximum contraction equal to about 70% of that induced by serotonin in the basilar artery. Ferrous Hb's (oxyHb and carboxyHb) produced much greater contraction than ferric Hb's (methemoglobin and cyanmethemoglobin), suggesting that superoxide radicals, an active species of oxygen, may be related to the contractile activity of Hb. Neither methysergide, phentolamine, mepyramine, nor aspirin inhibited the vasoconstrictive activity of oxyHb. This finding indicates that the activation of serotonergic, alpha-adrenergic, or histaminergic H1 receptors, or prostaglandin synthesis may not be involved in the mechanism of action of oxyHb. The constituents of Hb caused little or no contraction as compared with Hb as a whole. The basilar artery was more highly sensitive to Hb than arteries from other anatomical locations. Cyclic adenosine monophosphate caused a very slight decrease in the Hb-induced contraction. It is concluded that oxyHb can contract cerebral arteries in vitro. These results, coupled with recent reports on the participation of the RBC in producing chronic vasospasm, strongly suggest that oxyHb released from RBC's plays an important role in the pathogenesis of chronic cerebral vasospasm.

Endothelin-1 Gene Polymorphisms Influence Cerebrospinal Fluid Endothelin-1 Levels Following Aneurysmal Subarachnoid Hemorrhage

2014 ◽  
Vol 17 (2) ◽  
pp. 185-190 ◽  
Author(s):  
Matthew J. Gallek ◽  
Sheila A. Alexander ◽  
Elizabeth Crago ◽  
Paula R. Sherwood ◽  
Megan Klamerus ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Vasospasm ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Enzyme Linked Immunosorbent Assay ◽  
Exposure Rate ◽  
Positive Group ◽  
Endothelin 1 ◽  
Protein Levels ◽  
Angiographic Vasospasm

Aneurysmal subarachnoid hemorrhage is a type of stroke with high morbidity and mortality. Increased endothelin-1 (ET-1) levels have been associated with increased risk of cerebral vasospasm, which is associated with increased morbidity. The purpose of this study was to investigate the relationships between ET-1 genotypes and ET-1 protein levels in cerebrospinal fluid (CSF) measured 72 hr before angiographic vasospasm measurement in subjects at high risk of cerebral vasospasm. Specifically, this study evaluated the differences between variant positive and variant negative groups of nine different ET-1 single-nucleotide polymorphisms (SNPs) in relationship with the ET-1 protein exposure rate. The CSF ET-1 protein levels were quantified using enzyme-linked immunosorbent assay. One functional SNP and eight ET-1 tagging SNPs were selected because they represent genetic variability in the entire ET-1 gene. The variant negative group of SNP rs2070699 was associated with a significantly higher ET-1 exposure rate than the variant positive group ( p = 0.004), while the variant positive group of the rs5370 group showed a trend toward association with a higher ET-1 exposure rate ( p = 0.051). Other SNPs were not informative. This is the first study to show differences in ET-1 exposure rate 72 hr before angiography in relation to ET-1 genotypes. These exploratory findings need to be replicated in a larger study; if replicated, these differences in genotypes may be a way to inform clinicians of those patients at a higher risk of increased ET-1 protein levels, which may lead to a higher risk of angiographic vasospasm.

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