• International Journal of Industrial Entomology and Biomaterials
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• v.35 no.1
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• pp.39-44
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• 2017

The venome of Phoneutria nigriventer spider has been shown to have side effects including severe painful erections that last for hours. PnTx2-6, a toxin from P. nigriventer spider venom, modulates voltage gated $Na^+$ channels and activation of nitric oxide (NO) production. NO is essential for the regulation of blood flow and pressure. Therefore, PnTx2-6 is expected to be effective not only for erectile dysfunction but also for cardiovascular diseases. A previously has reported cDNA clone for PnTx2-6 toxin, which was expressed in E. coli cytoplasm. We created the same clone and expressed it in a bacterial expression system. PnTx2-6 increased the genes expression of superoxide dismutase 1, glutathione peroxidase 1, and sulfiredoxin 1. We hypothesized that recombinant PnTx2-6 may indirectly regulate blood flow and pressure, resulting in NO production in human umbilical vein endothelial cells (HUVEC). These data suggest differential regulation of the vascular ageing process, which may contribute to the anatomic heterogeneity of atherosclerosis. The results of this study may be used for the emergency treatment of sudden cardiovascular disease caused by ageing.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.5
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• pp.1335-1338
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• 2003

We have previously reported that the vasodilatory effect of BanhabackchuIChunma-tang(半夏白朮天麻湯; BCT), a herbal formula, and its mechanism might be associated with at least in part NO pathway. In the present study, we studied the influence of BanhabackchulChenuma-tang (BCT) on the phosphorylation of LC20, in parallel, the distribution of α-protein kinase C(PKCα) by phenylephrine was monitored using laser scan confocal immunofluorescent microscopy in freshly isolated ferret portal vein smooth muscle living single cells. Phenylephrine stimulation induced LC20 phosphorylation and translocation of PKCα. However, BCT dephosphorylated LC20 phosphorylation and inhibited the translocation of PKCα. Our results demonstrate that the mechanism of relaxant effect of BanhabackchulChunma-tang inhibition is associated with inhibition of PKCα activation and LC20 phosphorylation.

• Molecules and Cells
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• v.27 no.2
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• pp.191-198
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• 2009

The present study was undertaken to determine whether treatment with genistein, the plant-derived estrogen-like compound influences agonist-induced vascular smooth muscle contraction and, if so, to investigate related mechanisms. The measurement of isometric contractions using a computerized data acquisition system was combined with molecular experiments. Genistein completely inhibited KCl-, phorbol ester-, phenylephrine-, fluoride- and thromboxane $A_2$-induced contractions. An inactive analogue, daidzein, completely inhibited only fluoride-induced contraction regardless of endothelial function, suggesting some difference between the mechanisms of RhoA/Rho-kinase activators such as fluoride and thromboxane $A_2$. Furthermore, genistein and daidzein each significantly decreased phosphorylation of MYPT1 at Thr855 had been induced by a thromboxane $A_2$ mimetic. Interestingly, iberiotoxin, a blocker of large-conductance calcium-activated potassium channels, did not inhibit the relaxation response to genistein or daidzein in denuded aortic rings precontracted with fluoride. In conclusion, genistein or daidzein elicit similar relaxing responses in fluoride-induced contractions, regardless of tyrosine kinase inhibition or endothelial function, and the relaxation caused by genistein or daidzein was not antagonized by large conductance $K_{Ca}$-channel inhibitors in the denuded muscle. This suggests that the RhoA/Rho-kinase pathway rather than $K^+$- channels are involved in the genistein-induced vasodilation. In addition, based on molecular and physiological results, only one vasoconstrictor fluoride seems to be a full RhoA/Rho-kinase activator; the others are partial activators.

• The Korean Journal of Pharmacology
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• v.31 no.1 s.57
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• pp.27-37
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• 1995

In anesthetized rats, we examined the possibility that endothelium-derived relaxing factor (EDRF) or nitric oxide (NO) released in response to cholinergic mechanism may contribute to the reflex autoregulation of cerebral blood flow. Suffusion with mock cerebrospinal fluid (CSF), containing acetylcholine (ACh, $10^{-9}{\sim}10^{-6}M$) evoked concentration-dependent vasodilatation of the resting pial artery (mean, $19.3{\pm}1.7{\mu}m$, n=36), which was significantly inhibited not only by $N{\omega}$-nitro-L-arginine (L-NNA, $10^{-5}M$) but also by methylene blue ($10^{-6}M$) and oxyhemoglobin ($10^{-6}M$). The muscarinic receptors in the endothelium of pial artery implicated in the release of EDRF were considered to be $M_1\;and\;M_3$ subtypes. When suffused with mock CSF containing L-arginine it caused a transient vasodilatation, which was strongly inhibited by LY 83583 ($10^{-5}M$), but not by L-NNA ($10^{-5}M$). Additionally, both ACh- and L-arginine-induced vasodilation were significantly inhibited by glibenclamide, a specific ATP-sensitive $K^+$ channel blocker. On the other hand, changes in pial arterial diameter were plotted as a function of changes in systemic arterial blood pressure. The slopes of regression lines for vasodilation and vasoconstriction were not affected by pretreatment with $10^{-5}M$ L-NNA, but significantly reduced by $3{\times}10^{-6}M$ glibenclamide. Thus it is suggested that the reflex vasodilation of rat pial arteries in response to a transient hypotension is not mediated by EDRF (NO).

• Journal of Ginseng Research
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• v.23 no.4
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• pp.230-234
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• 1999

Potassium channels play an important role in regulating vascular smooth muscle tone. Four types of $K^+$ channels areknown to be expressed in vascular smooth muscle cells, and maxi $Ca^{2+}-activated\;K^+$ channel $(BK_{Ca})$ is a dominant type of $K^+$ channels in these cells. Because total ginseng saponins and ginsenoside $Rg_3$ cause vasodilation with unclear mechanisms, we hypothesized that total ginseng saponins and ginsenoside $Rg_3$ induce vasodilation via activation of maxi $Ca^{2+}-activated\;K+$ channels. Whole-cell BKe. currents were voltage-dependent with half maximum activation at -14 mV, and the currents were sensitive to nanomolar ChTX and millimolar TEA. External application of total ginseng saponins increased the anlplitude of the whole-cell BKe. current in a concentration-dependent manner. Single-channel analysis indicates that total ginseng saponins caused the channel opening for a longer period of time. Ginsenoside $Rg_3$ increased the amplitude of whole-cell $K_{Ca}$ currents without affecting voltage dependence of the currents and increased single-channel open time. Hence, the results suggest that ginseng saponin-induced vasodilation may be due to activation of $K_{Ca}$.

• Aerospace Engineering and Technology
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• v.9 no.1
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• pp.143-150
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• 2010

This study examined the effect of cold water finger immersion at various water temperature on cold-induced vasodilation (CIVD) and its reproducibility to the cold stress. Ten healthy collegiate men ($21.4{\pm}2.5$ yrs, $175.8{\pm}4.1$ cm, $69.6{\pm}7.6$ kg, $11.2{\pm}3.7$ %fat) underwent two tests. At the first test (1ST), subjects immersed their middle fingers at $43^{\circ}C$ water for 5 min followed by a resting at an ambient air for 25 min. Then they immersed the finger at one of the five water temperatures (Tw: 5, 8, 11, 14, or $17^{\circ}C$) at random order for 20 min. Once a testing at one Tw was completed, they immediately repeated the testing procedure for another Tw. The second test(2ND) was performed within a week after 1ST with having an identical procedure of 1ST except the order of Tw. During the test, rectal temperature, finger temperature from middle finger nail bed, and heart rate were measured every six second. In conclusion, maximal finger temperature(Tfmax), and Tfmax minus Tw was highly reproducible in this experiment. Minimal finger temperature (Tfmin) and Tfmax were higher as Tw decreased. And Tfdiff was higher as the colds tress decreased. No differences were found in time variables of temperature responses.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.203.2-204
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• 2003

Nitric oxide (NO) produced in large amounts by inducible nitric oxide synthase (iNOS) is known to be responsible for the vasodilation and hypotension observed in septic shock and inflammation. Inhibitors of iNOS, thus, may be useful candidate for the treatment of inflammatory diseases accompanied by the overproduction of NO. We prepared alcoholic extracts of woody plants and screened the inhibitory activity of NO production in lipopolysaccharide (LPS)-activated macrophages after the treatment of these extracts. (omitted)

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.22 no.3
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• pp.1-10
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• 2009

Purpose : The objective of present study is to detect the effect of Sopungsan aqueous extracts (SPS) on the passive cutaneous anaphylaxis (PCA; type I allergic dermatitis) Method : 500, 250 and 125mg/kg of SPS were orally administered 12 hr-interval before antigen challenge (total 4 times administered). PCA reactions were induced using rat anti-ovalbumin (OVA) serum contain IgE (titer 1:32) as sensitization and OVA as antigen challenge. 30 min after antigen challenge, the diameter of blue-dye spots (evans blue) and leaked amount of dye were observed with histology and histomorphometry at the PCA induced sites. In addition, serum total IgE and histamine levels were also observed by ELISA, respectively. The effects of SPS were compared with dexamethasone 1mg/kg treated rats in the present study. Results : As results of PCA reaction, vasodilation related increase of diameter of blue-dye spot and amount of leaked dye were observed with swelling and edematous changes in the dermis of PCA induced sites. However, these changes on PCA reactions were dramatically and dose-dependently decreased by treatment of SPS as compared with vehicle control. In addition, serum elevations of IgE and histamine were also dose-dependently inhibited by treatment of SPS as compared with vehicle control respectively. The effects of SPS 500mg/kg were similar to that of dexamethasone 1mg/kg in the present study. Conclusion : Base on the results of the present study, it is concluded that SPS has favorable effect on the PCA-induced allergic dermatitis, and SPS 500mg/kg showed similar favorable effects as compared with dexamethasone 1mg/kg. The present findings demonstrate that SPS can be effective for the prevention and treatment of allergic dermatitis.

• Journal of Korean Neurosurgical Society
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• v.57 no.1
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• pp.1-5
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• 2015

Objective : Cerebral vessels, such as intracerebral perforating arterioles isolated from rat brain, have been widely used as an ex vivo model to study the cerebrovascular function associated with cerebrovascular disorders and the therapeutic effects of various pharmacological agents. These perforating arterioles, however, have demonstrated differences in the vascular architecture and reactivity compared with a larger leptomeningeal artery which has been commonly implicated in cerebrovascular disease. In this study, therefore, we developed the method for studying cerebrovascular function utilizing the olfactory artery isolated from the mouse brain. Methods : The olfactory artery (OA) was isolated from the C57/BL6 wild-type mouse brain. After removing connective tissues, one side of the isolated vessel segment (approximately $-500{\mu}m$ in length) was cannulated and the opposite end of the vessel was completely sealed while being viewed with an inverted microscope. After verifying the absence of pressure leakage, we examined the vascular reactivity to various vasoactive agents under the fixed intravascular pressure (60 mm Hg). Results : We found that the isolated mouse OAs were able to constrict in response to vasoconstrictors, including KCl, phenylephrine, endothelin-1, and prostaglandin $PGH_2$. Moreover, this isolated vessel demonstrated vasodilation in a dose-dependent manner when vasodilatory agents, acetylcholine and bradykinin, were applied. Conclusion : Our findings suggest that the isolated olfactory artery would provide as a useful ex vivo model to study the molecular and cellular mechanisms of vascular function underlying cerebrovascular disorders and the direct effects of such disease-modifying pathways on cerebrovascular function utilizing pharmacological agents and genetically modified mouse models.

• Journal of Oral Medicine and Pain
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• v.9 no.1
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• pp.11-22
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• 1984

The authors administered KCN, NaF,AS2O3 orally to rabbits and caused acute and chronic poisoning, then studied the teeth, jaw bones, and other oral tissues histopathologically. The results were as follows : 1. There was no significant difference between acute poisoned group by NaF and control group. But, vasodilatation in the connective tissues, esepcially marginal area of jaw bone, atrophy and destrution of glandualr cells was observed. 2. Chronic poisoned group by NaF showed degeneration and thicking of subcutanece fibrosis ective tissues, atrophy and degeneration of subcutaneous connective tissues, atrophy and degeneration of muscle fibers, vasodilation of subcutaneous in bone cavities(lacunae), and degeneration of odotlblasts in pulp tissue. 3. Acute poisoned group by KCN showed almost similar appearances as control group, and chronic poisoned group showed hyperplasia of baal layer in epitheilium, degeneration of subcutaneous connective tissues, vasodilation and huperemia, severe hemorrhage of marginal area of jaw bone. hyperplasia of salivary gland ducts, but normal arrangement of muscle fibers and narrow bone carity(lacunae) due to active osteoblastic action, osteodentin were observed. 4. Acute poisoned group by AS2O3 showed degeneration of basal cell, atrophy of blood vessels in palatal muscosa. Chronic poisoned group showed irregular cell arrangement and degeneration, reduction of capillaries in palatal mucosa. Osteoclasts in jaw bone were observed. 5. In Masson's Trichrome and Van Gieson Staining, chronic poisoned group by NaF showed thicking and loosening of subcutaneous connective tissues. Hyperplasia of intermuscular connective tissue was observed in chronic poisoning by KCN and NaF. In PAS staining, negative reation in outer layer of palatalmucosa, positive reaction in keratin layer and mild reaction of basal layer in palate and tongue mucosa was observed.