• The Korean Journal of Pain
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• v.29 no.4
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• pp.229-238
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• 2016

Background: The goal of this in vitro study was to investigate the effect of lipid emulsion on vasodilation caused by toxic doses of bupivacaine and mepivacaine during contraction induced by a protein kinase C (PKC) activator, phorbol 12,13-dibutyrate (PDBu), in an isolated endothelium-denuded rat aorta. Methods: The effects of lipid emulsion on the dose-response curves induced by bupivacaine or mepivacaine in an isolated aorta precontracted with PDBu were assessed. In addition, the effects of bupivacaine on the increased intracellular calcium concentration ($[Ca^{2+}]_i$) and contraction induced by PDBu were investigated using fura-2 loaded aortic strips. Further, the effects of bupivacaine, the PKC inhibitor GF109203X and lipid emulsion, alone or in combination, on PDBu-induced PKC and phosphorylation-dependent inhibitory protein of myosin phosphatase (CPI-17) phosphorylation in rat aortic vascular smooth muscle cells (VSMCs) was examined by western blotting. Results: Lipid emulsion attenuated the vasodilation induced by bupivacaine, whereas it had no effect on that induced by mepivacaine. Lipid emulsion had no effect on PDBu-induced contraction. The magnitude of bupivacaine-induced vasodilation was higher than that of the bupivacaine-induced decrease in $[Ca^{2+}]_i$. PDBu promoted PKC and CPI-17 phosphorylation in aortic VSMCs. Bupivacaine and GF109203X attenuated PDBu-induced PKC and CPI-17 phosphorylation, whereas lipid emulsion attenuated bupivacaine-mediated inhibition of PDBu-induced PKC and CPI-17 phosphorylation. Conclusions: These results suggest that lipid emulsion attenuates the vasodilation induced by a toxic dose of bupivacaine via inhibition of bupivacaine-induced PKC and CPI-17 dephosphorylation. This lipid emulsion-mediated inhibition of vasodilation may be partly associated with the lipid solubility of local anesthetics.

• YAKHAK HOEJI
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• v.34 no.3
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• pp.180-191
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• 1990

A comparison was made of the effects of selective ${\alpha_1}-adrenoceptor$ agonist phenylephrine and selective ${\alpha_2}-adrenoceptor$ agonist clonidine on endothelium-containing and endothelium-denuded rings of the rat aorta. In the case of phenylephrine, removal of endothelium increased sensitivity 2.5 fold at $EC_{50}$ level and maximum contractive response 1.4 fold. In the case of clonidine, which gave only 15% of maximum contractive response given to phenylephrine on endothelium-containing rings, removal of the endothelium increased sensitivity 5.6 fold at $EC_{50}$ level and maximum contractive response 5 fold, which was about 55% of that given by phenylephrine. In endothelium-denuded ring, phenylephrine-induced contraction tended to be more increased in tonic contraction than in phasic contraction as compared to that in endothelium-containing ring, while clonidine-induced contraction was monophasic and was increased only in tonic contraction. In the calcium-free solution or in the presence, of verapamil, contraction stimulated by clonidine was almost abolished while that stimulated by phenylephrine produced only phasic contraction. The depression of sensitivity to these agonists in rings with endothelium appeared to be due to the vasodepressor action of endothelium derived relaxing factor (EDRF), because hemoglobin, a specific blocking agent of EDRF, abolished this depression. It is unlikely that the endothelium-dependent relaxation was due to stimulation of release of EDRF, because clonidine did not produce endothelium-dependent relaxation in 5-hydroxytryptamine-precontracted ring even when its contractile action was blocked by the ${\alpha_1}-adrenoceptor$ antagonist, prazosin. When the efficacy of phenylephrine was reduced to about the initial efficacy of clonidine by pretreatment with dibenamine, the contraction-response curves for phenylephrine became very similar to the corresponding curves obtained for clonidine before receptor inactivation. In the dibenamine-treated rings, contraction of phenylephrine was abolished in calcium-free solution or in the presence of verapamil like that obtained for clonidine before receptor inactivation. These results suggest that EDRF spontaneously released from endothelium depress contraction more profoundly in a case of an agonist with low efficacy and the phenylephrine-induced contraction was totally dependent on extracellular calcium as was that obtained for clonidine when the efficacy of phenylephrine was reduced to that of clonidine by irreversible inactivation of ${\alpha_1}-adrenoceptor$ with dibenamine.

• KSBB Journal
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• v.19 no.4
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• pp.274-283
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• 2004

Six lumbrokinase (LK) fractions from Lumbricus rubellus lysates were purified by a series of column chromatographies. The molecular weights of the six LK fractions appeared to range from 24.6 to 33.1 kDa. In the experimental model of rat venous thrombosis, the thrombus weight and PAI activity decreased significantly when the LK was administered orally. However, the activities of APTT, PT and plasmin showed a significant increase. The aggregation of rat platelets pretreated with various LK doses was inhibited by thrombin, and the MDA generation decreased. The rat thoracic aorta and mesentric arteries contracted with phenylephrine relaxed due to the treatment of the LK fractions. These results suggest that the fibrinolytic effects of LK were mediated not only by proteolytic activity, but also by the inhibition of platelet agregation and the relaxation of blood vessels. It is concluded that the LK may be useful as a hemolytic agent for treatment of fibrin clot.

• The Journal of Korean Medicine
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• v.34 no.3
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• pp.86-95
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• 2013

Objectives: Sprague-Dawley rats were fed with high fat diet, and atherogenic changes were seen in the aorta. However, when Sprague-Dawley rats were fed with a high fat diet and administered Youngyopaedoc-san together, these atherogenic changes were rarely seen. This study was aimed to find the inflammatory marker level changes in Sprague-Dawley rats with Youngyopaedoc-san-related anti-atherogenic effect. Methods: The extract from Youngyopaedoc-san was made by the pharmacy department of Kyung-hee Oriental Medical Hospital. The animals were divided into five groups: normal diet, high fat diet, high fat diet with Youngyopaedoc-san, high fat diet with Vytorin, and high fat diet with Youngyopaedoc-san and Vytorin. A light microscopic image of a cross section taken from the aorta of the Sprague-Dawley rat was analyzed. We compared inflammatory marker levels among the five groups. Results: The complex of Youngyopaedoc-san and Vytorin has more anti-atherogenic effects in the aorta of Sprague-Dawley rats fed with high fat diet than Vytorin alone. Youngyopaedoc-san has inhibitory effect on the increase of IFN-${\gamma}$ and IL-2 levels. The difference on eosinophil levels of each group was statistically significant, but the eosinophil level of each group was within normal limits, so the difference on eosinophil levels was not clinically significant. Conclusions: Youngyopaedoc-san-related anti-atherogenic effect could be a result of inhibitory mechanism on IFN-${\gamma}$ and IL-2.

• Journal of Nutrition and Health
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• v.25 no.6
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• pp.476-484
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• 1992

The influence of selenuium deficiency and fish oil on lipid peoxidation status and fatty acid composition of tissues(plasma aorta and liver) was studied. Male Sprague Dawley rats were fed for eight weeks semipurified diets containing 7% corn oil(by weight) or 5, 5% fish oil(MaxEPA) plus 1.5% corn oil with oil with or without selenium status (glutathione peroxidase activity and selenium levels) were significantly lower in the rats given inadequate selenium in plasma aorta (p<0.02 and p<0.001 respectively) gut not that in plasma Selenium supplementation decreased hepatic MDA levels(p<0.02) Increases in the levels of 20:5(n-3) 22:5(n-3), 22:6(n-3) 20:3(n-6) and a decrease in the level of 20:4(n-6) were observed in plasma total lipids and aortic and hepatic phospholipids when fish oil was fed. Though selenium supplementation increased the level of n-3 fatty acids(such as 22:6(n-3)) in plsama and the aorta is overall effect was smaller than the effect of fish oil feeding. These data suggest that selenium may play a significant but minor role in protecting against lipid peroxide-tion even when vitamin E intakes are in excess of current recommendations in both corn oil and fish oil diets.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.1
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• pp.84-92
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• 2004

The present study examined the effects of Taekunyukmijiwhang-tang (TV) on blood pressure and renal function in nitric oxide (NO)-dependent hypertensive rats. A phamacological inhibition of nitric oxide synthase (NOS) for 4-6 weeks produces renal vasoconstriction, renal dysfunction, and progressive severe hypertension. Treatment of rats with NG-Nitro-L-arginie methylester (L-NAME) (100 mg/L, 6 weeks), which is a nonspecific NOS inhibitor, cause a sustained increase in systolic blood pressure (SBP), along with the decrease in expression of ecNOS in the kidney and thoracic aorta. The expression of Na, K-ATPase α1 subunit in the kidney was also reduced in the L-NAME induced hypertensive rats group. The renal functional parameters including urine osmolality (Uosm), creatinine clearance (Ccr), which is an index of glomerular filtration (GFR) were decreased in rat with L-NAME induced hypertension. while solute-free water reabsoption (TcH₂O) was unchanged in all experimental group. However, the group combined treated with TV and L-NAME did not develop hypertension and expression of ecNOS in the aorta was restored. The expression of Na/sup +/, K/sup +/-ATpase α1 subunit in the kidney was markedly restored in L-NAME-induced hypertension rats by administration of TV along with the restoration of urinary volume (UV) and sodium excretion (UNaV), whlie Na/sup +/, K/sup +/-ATPase /β1 subunit was not altered. These results suggest that TV attenuates an increase in SSP in the L-NAME induced hypertension and restores partially renal function, which seems to be caused by up-regulation of expression of Na/sup +/, K/sup +/-ATPase α1 subunit in the kidney and ecNOS in thoracic aorta.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.1
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• pp.146-150
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• 2003

It had been known for a while that Crataegi Fructus(CF; Crataegus pinnatifida Bunge) had only a digestive effect. Recently, it has been demonstrated that CF also has an anti-hypertensive effect. However, its mechanism of relaxant effect has not been investigated yet. This study was examined to investigate the mechanism of vascular relaxation effect of CF in isolated rat thoracic aorta. CF revealed significant relaxation to phenylephrine(PE)-induced arterial contraction but much less to KCI-induced one. When CF was pretreated, it inhibited PE-induced contraction non-competitively. Methylene blue(10/sup -6/M) completely blocked the relaxant effect of CF whereas L-NAME(10/sup -5/M) did almost completely. However, atropine(10/sup -6/M) did not have any influence on vascular relaxation effect of CF. Regarding cNOS activity, CF significantly increased its activity from rat whole brain homogenate in a dose dependent manner which was inhibited by L-NAME(10/sup -5/M). On the other hand, CF did not affect on expression of TNF-α mRNA in RAW 264.7 cells, suggesting that CF is not related to iNOS activity. These results indicate that CF would be effective in relaxing vascular contraction through release of endothelial nitric oxide.

• Herbal Formula Science
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• v.28 no.3
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• pp.271-280
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• 2020

Hypertension has been approved to cause disharmony between the heart and kidney such as cardiac hypertrophy and kidney dysfunction. In traditional oriental medicine Paeo-tang (PET) has been shown to have effects on blood circulation improvement. However, the beneficial effect of PET on hypertension remains unknown. In this study, we investigated that PET attenuates blood pressure and improves cardiovascular and renal function in NG-nitro-L-arginine methylester (L-NAME) rat model. Hypertensive rat models were induced by the administration of L-NAME (40 mg/kg/day) and then PET (50 or 100 mg/kg/day) or Olmetec was treated for 2 weeks. PET treatment significantly suppressed the systolic blood pressure and decreased intima-media thickness in the thoracic aorta. PET ameliorated endothelium-dependent and independent vascular relaxation in the L-NAME-induced vascular dysfunction. PET ameliorated the functional decline in the kidney such as albumin and blood urea nitrogen in plasma. These results demonstrated that PET possesses protective effects against L-NAME-induced hypertension.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.2
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• pp.99-104
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• 2000

We investigated the action of NOS inhibitors on NOS in rats. Both of nitric oxide synthase inhibitors, $N^G$-monomethyl-L-arginine $(L-NMMA,\;3\;{\mu}M)$ or $N^G$-nitro-L-arginine methylester $(L-NAME,\;30\;{\mu}M),$ augmented phenylephrine $(PE,\;10^{-7}\;M)-induced$ contraction which was inhibited by acetylcholine (ACh) in rat thoracic aorta. This augmentation by L-NAME or L-NMMA was attenuated with the treatment of NO precursor, arginine. ACh, however, decreased the augmentation induced by L-NMMA, but not by L-NAME. Superoxide dismutase (SOD, 50 u/ml) potentiated an inhibitory effect of ACh on the PE $(10^{-7}\;M)-induced$ contraction. It has been known that platelet activating factor itself induces iNOS. Platelet activating factor $(PAF,\;10^{-7}\;M)$ inhibited PE $(10^{-7}\;M)-induced$ contraction. Pretreatment with L-NMMA (30 mM) or L-NAME (30 mM) significantly blocked the inhibitory action of PAF on PE-induced contraction. L-NMMA (100 mM) or L-NAME (100 mM) reduced nerve conduction velocity (NCV) relevant to nNOS in rat sciatic nerve. ACh attenuated the reduction of NCV by L-NMMA-, but not by L-NAME-induced reduction of NCV. These results suggest that L-NMMA and/or L-NAME have different action on three types of NOS in rats.

• Korean Journal of Acupuncture
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• v.27 no.1
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• pp.107-123
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• 2010

Objective & Methods: The purpose of this study is to investigate the effects of Artemisiae Capillaris Herba herbal-acupuncture (ACH-HA) at GB34 (Yangleungchean) on hyperlipidemia induced with alloxan injection and high fat diet in rats. The author performed several experimental items to analyze the levels of various components and enzymes in serum, liver, as well as the histological changes of liver and aorta. Results: 1. ACH-HA solution increased the DPPH radical scavenging activity in rat liver cells. 2. ACH-HA at GB34 significantly decreased the levels of serum total cholesterol, low-density lipoprotein (LDL)-cholesterol, free cholesterol and atherogenic index (AI), while significantly increased the ratios of high-density lipoprotein (HDL)/total cholesterol and phospholipid/total cholesterol in hyperlipidemic rats. 3. ACH-HA at GB34 significantly decreased serum aspartate aminotransferase (AST) level in hyperlipidemic rats. 4. ACH-HA at GB34 significantly increased hepatic glutathione (GSH) activity in hyperlipidemic rats. Conclusion: From the above results, it is suggested that ACH-HA at GB34 may have therapeutic and preventive effects on hyperlipidemia.