• Journal of Veterinary Clinics
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• 제35권3호
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• pp.114-118
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• 2018

A 3-month-old intact male Lakeland terrier was presented with recurring regurgitation after removing cervical esophageal foreign body by endoscopy. Blood and urine analysis, radiography, ultrasonography, fluoroscopic esophagography, computed tomographic angiography (CTA) were performed. In radiography and fluoroscopic esophagography, vascular ring anomaly was considered as the primary cause of megaesophagus, and CTA with gas-inflation of the esophagus was performed. Compressed esophagus, persistent right aortic arch (PRAA), aberrant left subclavian artery (LSA), and a venous structure which was confirmed in surgery to be incomplete type persistent left cranial vena cava (PLCVC) connected with the left side azygos vein were observed. Left deviation of the trachea was also revealed in CT, which implies the compression by left ligamentum arteriosum. Therefore, type 3 PRAA with left ligamentum arteriosum and aberrant LSA, was considered as a prior differential diagnosis. Surgical repair was performed and the clinical signs improved. This report describes CTA characteristics of combination of PRAA with aberrant LSA, incomplete PLCVC and Lt. azygos vein in a dog. Although not every vascular anomaly does induce clinical sign, some types can complicate the surgical procedure, and cause clinical signs. Therefore, thorough evaluation of vascular anomalies in the thorax is important, and CTA is a useful method in identifying multiple vascular anomalies in dogs.

• Bulletin of the Korean Chemical Society
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• 제30권9호
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• pp.2083-2086
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• 2009

Human vascular endothelial growth factor receptor 2 (hVEGFR2) is an important signaling protein involved in angiogenesis and attractive drug target in cancer therapy. It has been reported that flavonols, a class of flavonoids, have anti-angiogenic activity in various cancer cell lines. We performed receptor-oriented pharmacophore based in silico screening for identification of hVEGFR2 inhibitors from flavonol database. By comparing with three X-ray complex structures of hVEGFR2 and its inhibitors, we evaluated the specific interactions between inhibitors and receptors and determined a single pharmacophore map. This map consisted of four features, a hydrogen bonding acceptor (HBA) on Cys917, two hydrogen bonding donors on Glu917 (HBD1) and Glu883 (HBD2), and one hydrophobic interaction (Lipo) with Val846, Ala864, Val897, Val914 and Phe1045 of hVEGFR2. Using this map, we searched a flavonol database including 9 typical flavonols and proposed that five flavonols, kaempferol, quercetin, fisetin, morin, and rhamnetin can be potent inhibitors of hVEGFR2. 3-OH of C-ring and 4’-OH of B-ring of flavonols are the essential features for hVEGFR2 inhibition. This study will be helpful for understanding the mechanism of inhibition of hVEGFR2 by natural products.

• Journal of Chest Surgery
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• 제9권2호
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• pp.251-264
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• 1976

Forty three patients with disease of the aorta were admitted in this department during the period from beginning of 1956 to the end of 1976. They consisted of eighteen cases of aortic aneurysms, eight cases of Takayasu's arteritis, eight Leriche syndromes, six dissecting aneurysms, two aortic coarctations and one case of vascular ring. Of eighteen aortic aneurysms, twelve were operated resulting in eight survivors. Three of four mortalities were in shock preoperatively because of aneurysmal rupture. Among six dissecting aortic aneurysms, four were type III and two were type I according to DeBakey's classification. For the purpose of relief of acute arterial insufficiency in the lower extremities, a re-entry operation grafting a Y-shaped dacron vessel between abdominal aorta and common iliac arteries was performed. The patient regained consciousness soon after the operation and was well until postoperative second day, when severe convulsion developed abruptly and died. And in a chronic case of type III dissecting aneurysm, a dacron graft bypass shunt between ascending aorta and lower descending thoracic aorta with resection of the aneurysm was performed, but acute severe aortic insufficiency developed soon after the operation and fell into intractable heart failure resulting in death. The cause of the aortic insufficiency seems to be retrograde dissection from the proximal anastomosis site in the ascending aorta. Three cases were treated medically with Wheat's regimen. Two of them survived with relief of symptoms. Eight patients of Takayasu's arteritis were all females and aged between twenty and forty-four averaging twenty nine. Bypass graft operation between aortic arch and carotid arteries using Y-shaped nylon prostheses were performed in three patients resulting in death in two cases postoperatively due to severe cerebral arterial insufficiency during the procedure. All the patients with Leriche syndrome were males and over forty. In two cases, bypass graft with Y-shaped dacron vessel between terminal aorta and common iliac or femoral arteries were performed with good result. Thromboembolectomy or thromboendarterectomy was employed in three patients, of whom one was aggravated in sexual problem postoperatively. One out of two aortic coarctations and a vascular ring were treated surgically with excellent results.

• Biomolecules & Therapeutics
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• 제27권5호
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• pp.474-483
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• 2019

Vascular endothelial growth factor (VEGF) plays a pivotal role in pathologic ocular neovascularization and vascular leakage via activation of VEGF receptor 2 (VEGFR2). This study was undertaken to evaluate the therapeutic mechanisms and effects of the tetrapeptide Arg-Leu-Tyr-Glu (RLYE), a VEGFR2 inhibitor, in the development of vascular permeability and choroidal neovascularization (CNV). In cultured human retinal microvascular endothelial cells (HRMECs), treatment with RLYE blocked VEGF-A-induced phosphorylation of VEGFR2, Akt, ERK, and endothelial nitric oxide synthase (eNOS), leading to suppression of VEGF-A-mediated hyper-production of NO. Treatment with RLYE also inhibited VEGF-A-stimulated angiogenic processes (migration, proliferation, and tube formation) and the hyperpermeability of HRMECs, in addition to attenuating VEGF-A-induced angiogenesis and vascular permeability in mice. The anti-vascular permeability activity of RLYE was correlated with enhanced stability and positioning of the junction proteins VE-cadherin, ${\beta}$-catenin, claudin-5, and ZO-1, critical components of the cortical actin ring structure and retinal endothelial barrier, at the boundary between HRMECs stimulated with VEGF-A. Furthermore, intravitreally injected RLYE bound to retinal microvascular endothelium and inhibited laser-induced CNV in mice. These findings suggest that RLYE has potential as a therapeutic drug for the treatment of CNV by preventing VEGFR2-mediated vascular leakage and angiogenesis.

• YAKHAK HOEJI
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• 제37권2호
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• pp.163-171
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• 1993

In order to study the functions of vascular endothelial nitric oxide(NO) generating system, we examined the effects of monomethylarginine(MMA) and dimethylarginine(DMA)(asym., sym.), arginine analogues, on modulation of vascular tone. Also, the concentrations of endogenous arginie and MMA were measured by HPLC in rat aortic tissues. The results were as follows. 1. The maximum relaxation induced by Ach (1.5$\times$10$^{-6}$M) was 80% of the contractility of rings of rat aorta induced by phenylephrine and L-Arg causes endothelium-dependent relaxation of the aorta precontracted with phenylephrine and these relaxation were concentration-dependent. 2. Endothelium-dependent contractility of rings of rat aorta induced by MMA (100 $\mu{M}$), DMA (asym., 100 $\mu{M}$) and DMA (sym., 100 $\mu{M}$) were 25.5%, 27.5% and 16.5% of that induced by phenylephrine respectively. 3. The relaxation of rat aortic ring induced by L-Arg was inhibited by MMA, DMA(asym.) and DMA(sym.). The degrees of inhibition induced by MMA, DMA(asym.) and DMA(sym.) were 45.7%, 37.1% and 18.3%, respectively. 4. The endogenous arginine and monomethylarginine contents in rat aorta were 83 pmoles/mg wet tissue, and 34.9 pmoles/mg wet tissue. After stimulation with Ach, the concentrations of L-Arg and MMA were significantly decreased. These results suggest that there are the strong relationships between the endogenous L-Arg and methylated arginines and NO-generating system.

• Journal of Veterinary Clinics
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• 제35권1호
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• pp.26-29
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• 2018

A 6-month-old, female poodle presented with a three-month history of persistent regurgitation immediately after eating. On physical examination, the patient was emaciated and dehydrated. Thoracic radiography showed ventral displacement of the trachea and increased radiopacity in the mediastinum, cranial to the heart base. A severely dilated esophagus was identified cranial to the heart on esophagram. Computed tomography (CT) revealed the esophagus was filled with gas, fluid and a little of contrast and dilated from caudo-cervical to cranio-thoracic part. The esophageal diameter was markedly decreased at the heart base. In addition, the trachea was displaced to the left-ventral side of the right aortic trunk and an aberrant left subclavian artery originating from the aorta was identified. There was no evidence of abdominal vascular anomaly. Based on diagnostic imaging, persistent right aortic arch (PRAA) with an aberrant left subclavian artery was diagnosed. The patient did not undergo surgery and died at 15 days after diagnosis. This report describes imaging diagnosis, including CT and radiography in a weaned dog with regurgitation due to esophageal obstruction by PRAA. When PRAA is suspected and conventional radiography or contrast study is insufficient for diagnosis, CT may be helpful for diagnosing PRAA.

• The Korean Journal of Physiology and Pharmacology
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• 제4권6호
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• pp.463-469
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• 2000

It has been well known that 4-aminopyridine (4-AP) has an excitatory effect on vascular smooth muscle due to causing membrane depolarization by blocking $K^+-channel$. However, we observed that 4-AP had an inhibitory effect on the mesenteric artery of rat. Therefore, we investigated the mechanism of 4-AP-induced vasorelaxation. The mesenteric arcuate artery and its branches were isolated and cut into ring. The ring segment was immersed in HEPES-buffered solution and its isometric tension was measured. 4-AP $(0.1{\sim}10\;mM)$ induced a concentration-dependent relaxation, which was unaffected by NO synthase inhibitor, $N^G-nitro-L-arginine$ methylester $(100\;{\mu}M)$ or soluble guanylate cyclase inhibitor, methylene blue $(100\;{\mu}M).$ Glibenclamide $(100\;{\mu}M)$, ATP-sensitive $K^+$ channel blocker, did not exert any effect on the 4-AP-induced vasorelaxation. 4-AP relaxed the sustained contraction induced by 100 mM $K^+$ or $Ca^{2+}$ ionophore, A23187 $(100\;{\mu}M)$ in a dose-dependent manner. In addition, 4-AP significantly decreased the phasic contractile response to norepinephrine in the absence of extracellular $Ca^{2+}$. However, 4-AP did not block the $^{45}Ca$ influx of rat aorta. From the above results, we suggest that 4-AP may not block the $Ca^{2+}$ influx through $Ca^{2+}-channel,$ but act as a nonspecific vasorelaxant in arterial smooth muscle.

• YAKHAK HOEJI
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• 제45권1호
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• pp.78-84
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• 2001

Heme oxygenase is a rate-limiting enzyme in heme catabolism that cleaves heme to form biliverdin, iron, and carbon monoxide. Heme oxygenase-1 is expressed in many types of cells and tissues and is highly induced in response to oxidative stress. Carbon monoxide, one of the products of heme oxygenase, can stimulate soluble guanylate cyclase and dilate the vascular smooth muscle. So, the induction of heme oxygenase by lipopolysaccharide (LPS)-induced oxydative stress and the effect of the resultant carbon monoxide on aortic contractility were examined in this study. Zinc protoporphyrine IX (ZnPP), a inhibitor of heme oxygenase, elicited weak contraction of thoracic aortic ring, and this effect was more potent in aorta of LPS-treated rats than control and was blocked by methylene blue. The hyperreactivity to ZnPP in LPS-treated group was blocked by co-treatment with aminoguanidine. In the aortic ring of LPS-treated rats, ZnPP didn't change the vasoreactivity to phenylephrine or acetylcholine. ZnPP elicited hyper-tensive effect in concious rats, and pretreatment with LPS did not affect this effect. Prazosin significantly diminished the hypertensive effect of ZnPP. These results indicate that LPS induced heme oxygenase in aotra, and the resultant carbon monoxide diminished the aortic reactivity to vasoconstrictor.

• The Korean Journal of Physiology
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• 제27권2호
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• pp.199-207
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• 1993

To study the underlying mechanism through which the endothelium-dependent relaxation is inhibited by blocking the $Na^+\;-K^+$ pump, the effects of $Na^+\;-K^+$ pump blockade on the release of EDRF and its relaxing activity were examined, using organ bath study, bioassay technique, and cGMP measurement. Endothelium-dependent relaxation was attenuated by blocking the $Na^+\;-K^+$ pump in the vascular ring with intact endothelium. In bioassay experiment EDRF release was decreased with the blockade of the $Na^+\;-K^+$ pump in the EDRF donor strip. Endothelium-dependent increase of cGMP level was suppressed by inhibiting the $Na^+\;-K^+$ pump in the test strips. The magnitude of relaxation of test strip which was induced by the perfusate that had passed through the EDRF donor strip was decreased with the blockade of the $Na^+\;-K^+$ pump in the test strip. Therefore, it could be suggested that the attenuation of endothelium-dependent relaxation caused by inhibiting $Na^+\;-K^+$ pump activity is due to both the decreased release of EDRF from endothelial cells and the decreased sensitivity of the smooth muscle cells to EDRF.

• Molecules and Cells
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• 제23권2호
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• pp.175-181
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• 2007

The present study was undertaken to determine whether $SM22{\alpha}$ participates in the regulation of vascular smooth muscle contractility using $SM22{\alpha}$ knockout mice and, if so, to investigate the mechanisms involved. Aortic ring preparations were mounted and equilibrated in organ baths for 60 min before observing contractile responses to 50 mM KCl, and then exposed to contractile agents such as phenylephrine and phorbol ester. Measurement of isometric contractions using a computerized data acquisition system was combined with molecular or cellular experiments. Interestingly, the aortas from $SM22{\alpha}$-deficient mice ($SM22^{-/-LacZ}$) displayed an almost three-fold increase in the level of $SM22{\beta}$ protein compared to wild-type mice, but no change in the levels of caldesmon, actin, desmin or calponin. $Ca^{2+}$-independent contraction in response to phenylephrine or phorbol ester was significantly decreased in the $SM22{\alpha}$-deficient mice, whereas in the presence of $Ca^{2+}$ neither contraction nor subcellular translocation of myosin light chain kinase (MLCK) in response to phenylephrine or 50 mM KCl was significantly affected. A decrease in phosphorylation of extracellular signal regulated kinase (ERK) 1/2 was observed in the $SM22{\alpha}$-deficient mice and this may be related to the decreased vascular contractility. Taken together, this study provides evidence for a pivotal role of $SM22{\alpha}$ in the regulation of $Ca^{2+}$-independent vascular contractility.