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Studies on Digitalis Receptor Desensitization in Rat Ventricle

  • Lee, Shin-Woong-;Jang, Tae-Soo
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.04a
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    • pp.301-301
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    • 1994
  • $^3$H〕Ouabain binding parameters(K$\_$D/ and B$\_$max/,) in homogenates prepared fpom control rat ventricular strip and Langendorff preparations which were not previously exposed to ouabain were compared to those in homogenates from ventricular strip and Langendorff preparations that had been first exposed to a complete ouabain dose-response curve(10$\^$-7/M to 10$\^$-4/ M). In rat ventricular strips and Langendorff perfused rat heart preparations, cumulative dose-response cruves of ouabain revealed biphasic positive inotropic effects, a "low-dose" and a "high-dose" effect with ED$\_$50/ values of 0.5${\mu}$M and 35${\mu}$M ouabain, respectively- The "low-dose" effect in rat ventricular strips disappeared or was diminished significantly when the ouabain dose-response curve wag repeated after the washout of the effects of the first curve, whereas the maximal "high-dose" effect was identical in both exposures to oubain. However, there was no change in the "low-dose" effects in both sets of the Langendorff perfused hearts. The contractile activity of the pre-exposed strips did not indicate the presence of residual ouabain since their basal contractile force was decreased 10% compared to initial control. 〔$^3$H〕Ouabain binding parameters, K$\_$D/ and B$\_$max/, were not changed comparing homogenate of control ventricular strips with that of strips pre-exposed to ouabain. These results suggest that digitalis receptor desensitization in the rat ventricular strip may due to the change of post-receptor events induced by ouabain binding to a high affinity site(${\alpha}$$_2$ isoform).

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Impaired angiogenesis in the enalapril-treated neonatal rat kidney

  • Yim, Hyung Eun;Yoo, Kee Hwan;Bae, Eun Soo;Hong, Young Sook;Lee, Joo Won
    • Clinical and Experimental Pediatrics
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    • v.59 no.1
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    • pp.8-15
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    • 2016
  • Purpose: Nephrogenesis is normally accompanied by a tightly regulated and efficient vascularization. We investigated the effect of angiotensin II inhibition on angiogenesis in the developing rat kidney. Methods: Newborn rat pups were treated with enalapril (30 mg/kg/day) or vehicle (control) for 7 days after birth. Renal histological changes were checked using Hematoxylin & Eosin staining. We also investigated the intrarenal expression of vascular endothelial growth factor (VEGF)-A, VEGF receptor 1 (VEGFR1), VEGFR2, platelet-derived growth factor (PDGF)-B, and PDGF receptor-${\beta}$ with Western blotting and immunohistochemical staining at postnatal day 8. Expression of the endothelial cell marker CD31 was examined to determine glomerular and peritubular capillary density. Results: Enalapril-treated rat kidneys showed disrupted tubules and vessels when compared with the control rat kidneys. In the enalapril-treated group, intrarenal VEGF-A protein expression was significantly higher, whereas VEGFR1 protein expression was lower than that in the control group (P<0.05). The expression of VEGFR2, PDGF-B, and PDGF receptor-${\beta}$ was not different between the 2 groups. The increased capillary CD31 expression on the western blots of enalapril-treated rat kidneys indicated that the total endothelial cell protein level was increased, while the cortical capillary density, assessed using CD31 immunohistochemical staining, was decreased. Conclusion: Impaired VEGF-VEGFR signaling and altered capillary repair may play a role in the deterioration of the kidney vasculature after blocking of angiotensin II during renal development.

Relatoinship between Sarcoplasmic Reticular Calcium Release and $Na^+-Ca^{2+}$ Exchange in the Rat Myocardial Contraction

  • Kim, Eun-Gi;Kim, Soon-Jin;Ko, Chang-Mann
    • The Korean Journal of Physiology and Pharmacology
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    • v.4 no.3
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    • pp.197-210
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    • 2000
  • Suppressive role of $Na^+-Ca^{2+}$ exchange in myocardial tension generation was examined in the negative frequency-force relationship (FFR) of electric field stimulated left atria (LA) from postnatal developing rat heart and in the whole-cell clamped adult rat ventricular myocytes with high concentration of intracellular $Ca^{2+}$ buffer (14 mM EGTA). LA twitch amplitudes, which were suppressed by cyclopiazonic acid in a postnatal age-dependent manner, elicited frequency-dependent and postnatal age-dependent enhancements after $Na^+-reduced,\;Ca^{2+}-depleted$ (26 Na-0 Ca) buffer application. These enhancements were blocked by caffeine pretreatment with postnatal age-dependent intensities. In the isolated rat ventricular myocytes, stimulation with the voltage protocol roughly mimicked action potential generated a large inward current which was partially blocked by nifedipine or $Na^+$ current inhibition. 0 Ca application suppressed the inward current by $39{\pm}4%$ while the current was further suppressed after 0 Na-0 Ca application by $53{\pm}3%.$ Caffeine increased this inward current by $44{\pm}3%$ in spite of 14 mM EGTA. Finally, the $Na^+$ current-dependent fraction of the inward current was increased in a stimulation frequency-dependent manner. From these results, it is concluded that the $Ca^{2+}$ exit-mode (forward-mode) $Na^+-Ca^{2+}$ exchange suppresses the LA tension by extruding $Ca^{2+}$ out of the cell right after its release from sarcoplasmic reticulum (SR) in a frequency-dependent manner during contraction, resulting in the negative frequency-force relationship in the rat LA.

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A Comparative Study on Effects of Kyungohkgo and Kyungohkgo Ga Nokyong on Growth in Growth Deficiency Rat with Insufficient Nutrition Diet (성장장애 흰쥐에서 경옥고(瓊玉膏)와 경옥고가록용(瓊玉膏加鹿茸)의 성장효과 비교 연구)

  • Cha, Yun-Yeop
    • Journal of Korean Medicine for Obesity Research
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    • v.9 no.1
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    • pp.59-69
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    • 2009
  • Objectives This study was designed to evaluate the difference of between Kyungohkgo and Kyungohkgo Ga Nokyong effects of growth Methods We divided male Spraque-Dawley rats into 6 groups. They were Normal group, Growth deficiency rat with insufficient nutrition diet group, Growth deficiency rat with 0.1% Kyungohkgo group, Growth deficiency rat with 0.2% Kyungohkgo group, Growth deficiency rat with 0.1% Kyungohkgo Ga Nokyong group and Growth deficiency rat with 0.2% Kyungohkgo Ga Nokyong group. They were administered for 5 weeks. We measured body weight, serum growth hormone, insulin-like growth factor and thyroid stimulating hormone, RBC, concentration of Hb and PCV ratio, total WBC and its composition, the values of plasma glutamic oxaloacetic transaminase(GOT) and glutamic pyruvic transaminase(GPT) activities. Results 1. In body weight, Kyungohkgo 0.1%, Kyungohkgo Ga Nokyong 0.1%, 0.2% groups were showed sighnificantly different than control group. But That groups were not showed significantly different than each others. 2. In serum growth hormone, insulin-like growth factor and thyroid stimulating hormone, we obtained the results of tendency to increase in Kyungohkgo Ga Nokyong group, however these values showed no significantly different. 3. In the counts of RBC, Kyungohkgo group and Kyungohkgo Ga Nokyong group were showed significantly different than control group. But these values showed no significantly different. In the concentration of Hb, Kyungohkgo Ga Nokyong 0.2%group was showed significantly different than control group. Kyungohkgo Ga Nokyong 0.2% group and Kyungohkgo 0.2% group were showed significantly different than control group. 4. The counts of total WBC and its composition showed no significantly different in all treatment groups. 5. The values of plasma glutamic oxaloacetic transaminase(GOT) and glutamic pyruvic transaminase(GPT) activities showed no significantly different in all treatment groups. Conclusions So Kyungohkgo Ga Nokyong and Kyungohkgo have an effect of promoting growth of rats. And We know that the effect of Kyungohkgo Ga Nokyong is better than Kyungohkgo.

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Characterization of rat mammary epithalial cells and expression of gap junctional proteins (랫드 유선 상피 세포의 분리와 gap junction 단백질의 발현 양상)

  • Seo, Min-Soo;Kang, Kyung-Sun;Lee, Yong-Soon
    • Korean Journal of Veterinary Research
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    • v.43 no.4
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    • pp.649-656
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    • 2003
  • We have a cultured method to grow rat mammary epithelial cells (RMEC) for 1 to 14 days in 1:1 mixture of Dulbecco's Modified Eagle Medium: Nutrient and F-12 (DMEM/F-12) containing 10% fetal bovine serum (FBS), human EGF, insulin, hydrocortisone, human transferrin and $17{\beta}$-estradiol in vitro. We were able to isolate and distinguish two cell types, luminal epithelial cells and myoepithelial cells, from primary clutures of RMEC. Immunocytochemical stains were used to distingusih luminal epithelial cells and myoepithelial cells. Peanut lectin (PNA) was stained in most alveolar epithelail cells and luminal epithelial cells of rats, while Thy-1.1, a maker of potential rat mammary myoepithelial cells, was expressed in myoepithelial cells in the rat. Also, we examined the expression patterns of three types of gap junction proteins, connexin 26 ($C{\times}26$), connexins 32 ($C{\times}32$) and connexin 43 ($C{\times}43$) by immunocytochemistry and western blot analysis. In the cell types, the results show that at the early stage of culture, luminal epithelial cells were increased and these cells were surrounded by myoepithelial cells. At the late stage of culture, luminal epithelial cells were decreased, in contrast myoepithelial cells were increased. In the expression pattern of gap junction, $C{\times}26$ maintained it's expression until day 3, but afterwards gradually decreased in intensity. Expression of $C{\times}32$ remained until day 5, then decreased slightly. $C{\times}43$ gradually increased untill the middle time of culture then decreased in intensity. These results suggest that connexins may be important for the control of growth in rat mammary epithelial cell types.

Effects of Sopoongtang on the Cardiovascular System in the Experimental Animals (소풍탕(疎風湯)이 실험동물(實驗動物)의 심혈관계(心血管系)에 미치는 영향(影響))

  • Jeong, Jang-Gyun;Mun, Byeong-Sun
    • The Journal of Internal Korean Medicine
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    • v.16 no.1
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    • pp.197-213
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    • 1995
  • The present experiment was desinged to investigate the effects of Sopungtang water extracts on the Cardiovascular System in the Experimental Animals. Thus, the changes of blood pressure and heart rate were measured after oral administration. Measurments of Mortality rate were observed for measuring the effect of Sopungtang water extract. Sopungtang water extract against pulmonary thromboembolism induced by collagen the mixture(0.1ml/10g, 2mg/kg B.W) plus serotonin(5mg/kg B.W) in mouse. The effects of Sopungtang water extract were examined by observing the change of collagen-induced platelet aggregation, coagulation activity, ex vivo and in vitro fibrinolytic activity of euglobulin fraction in rats. The results were summarized as followings. 1. Sopungtang dropped the blood pressure in spontaneous hypertensive rat. 2. The drug increased the auricular blood flow in rabbit. 3. The drug relaxed the artery contraction by pretreated norepinephrine in rat. 4. The drug inhibited the death rate of mouse which was led to thromboembolism by serotonin and collagen. 5. The drug inhibited the platelet aggregation in rat. 6. The drug prolonged the prothrombin time and activated partial thromboplastin time on the test of plasma coagulation factor activity in rat, but was not valuable. 7. The drug increased the antithrombin activity in rat and the fibrinogen lyses time was reduced and lyses area was increased. 8. Sopungtang reduced fibrinogen lyses time of rat in vitro assay. According to the above mentioned results, Sopungtang increased the blood flow and dropped the blood pressure by the dilation of blood vessel. And the drug presented the antithrombin acivity, inhibited the platelet aggregation.

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Inhibition of Fat-Storing Cell Proliferation by a Monomeric Arginase Derived from Perfused Rat Liver

  • Kim, Ki-Yong;Choi, In-Pyo;Kim, Soung-Soo
    • BMB Reports
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    • v.33 no.3
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    • pp.213-220
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    • 2000
  • A fulminant hepatitis is associated with massive liver cell necrosis and a high mortality rate. But survivors regenerate a normal liver and do not have chronic liver disease. This clinical course suggests that the acutely injured livers release a factor that allows a recovery from chronic hepatitis or cirrhosis. The objective of this study was to isolate and characterize an anti-fibrotic factor from acutely damaged rat livers. The liver cell necrosis was prepared from rat by warm ischemical perfusion and the perfusates were assessed against the growth inhibition of fat-storing cells (FSC). A liver-derived growth inhibitory factor (LDGIF) was purified from ischemically damaged rat livers by chromatographies on Sephacryl S-300, CM Sepharose, hydroxyapatite, and Superose 12. The LDGIF was isolated with an overall purification of 194-fold and 40% recovery. Although LDGIF was identified as the rat liver arginase by Nterminal sequence analysis, LDGIF exists as a monomer and the purified native arginase has a trimer form. Furthermore, LDGIF has a lower enzyme activity on the hydrolysis of L-arginine and a higher inhibitory effect on proliferation of FSC than the normal rat liver arginase. The catalytic activity of LDGIF is ascribed to the monomeric characteristics of the LDGIF. Therefore, the inhibitory action of LDGIF might not be due to the arginine depletion by the catalytic activity of arginase. In conclusion, the presence of the LDGIF could interpret the clinical course that serious fibrosis is not found in the liver of patients recovering from severe hepatic necrosis due to fulminant hepatitis, suggesting that this LDGIF may provide a novel target for the prevention and treatment of hepatic fibrosis.

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A Comparative Study of Sepiae Os, Arcae Concha, Ostreae Concha and Esomeprazole in a Mouse Model of Reflux Esophagitis (역류성 식도염 생쥐 모델에서 해표초, 와릉자, 모려와 Esomeprazole의 치료효과에 대한 비교 연구)

  • Song, Chang-Hun;Baek, Tae-Hyun
    • The Journal of Korean Medicine
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    • v.39 no.2
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    • pp.92-105
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    • 2018
  • Objectives: This aim of this study is to compare the reflux esophagitis improvement effects of Sepiae Os, Arcae Concha, Ostreae Concha, and Proton Pump Inhibitor(esomeprazole) through rat experiments. Methods: NO production inhibitory effect was measured by NO production amount and iNOS mRNA expression level in cell lines. iNOS, $TNF-{\alpha}$ and $p-I{\kappa}B$, and serotonin were compared using immunohistochemistry at the rat reflux esophagitis. Reflux esophagitis connection external form, lower esophageal sphincter, and gap were observed and an esophageal inflammatory indicator, IL-6 activity was also evaluated by immunohistochemistry. Results: NO production and iNOS mRNA expression was showed concentration dependent decrease in cell lines treated with Sepiae OS, Arcae Concha, and Ostreae Concha at the experiments of cell lines. In the suppression of iNOS and $p-I{\kappa}B$ at the rat reflux esophagitis, Sepiae Os treat group(SOT) and Ostreae Concha treat group(OCT) were more effective. In the increase of serotonin at the rat reflux esophagitis, ACT, MT and OCT were more effective. Damage of lower esophageal sphincter, and gap between esophageal keratin and mucosa were observed less at the SOT, ACT, OCT. In the suppression of IL-6 at the rat reflux esophagitis, SOT and OCT were more effective than GE and, SOT was more effective than MT significantly. Conclusions: The anti-inflammatory effect was the best in the SOT and lower esophageal sphincter muscle contraction was the best in the ACT at the rat reflux esophagitis. Sepiae OS was more effective than esomeprazole in the suppression of iNOS, $TNF-{\alpha}$, and IL-6.

Further Investigation of the Action Mechanism of GS 389: a Thromboxane $A_2$ Antagonistic Action

  • Noh, Hong-Ki;Chang, Ki-Churl
    • Biomolecules & Therapeutics
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    • v.3 no.2
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    • pp.143-148
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    • 1995
  • Recently, we reported that GS 389 has vasodilating action without cardiac inotropic action (Chang et al., Can. J. Physiol. Pharmacol. 72, 327-334, 1994). However the mechanism of action of GS 389 has not been thoroughly evaluated. In the present study, we performed functional study of GS 389 in rat trachealis, thoracic aorta, pig coronary artery by isometric tension and in human platelets by aggregation experiments. We also tested if GS 389 influences on $Ca^{2+}$movement and inositol phosphate metabolism. In rat trachealis, GS 389 concentration-dependently relaxed carbachol (0.1 $\mu$M)- and high $K^{+}$(65.4 mM)-induced contraction with p$IC_{50}$/ of 4.43$\pm$ 0.19 and 4.11$\pm$0.12, respectively. In $Ca^{2+}$-free media, GS 389 inhibited carbachol-induced phasic contraction. In rat thoracic aorta, GS 389 inhibited $^{45}$ Ca uptake due to norepinephrine and high $K^{+}$, indicating that GS 389 has direct inhibitory action of $Ca^{2+}$movement. Furthermore, GS 389 competitively inhibited U46619-induced contraction in rat thoracic aorta and pig coronary artery with K, values of 5.23$\pm$0.12 and 5.56$\pm$0.14, respectively, and inhibited U 46619-induced phosphatidylinositide (PI) turnover in rat aorta. GS 389 also concentration-dependently inhibited the human platelet aggregation against U 46619 with p$IC_{50}$/ 5.66$\pm$0.02. These results indicate that GS 389 has thromboxane $A_2$ antagonistic action in vascular and platelets as well as direct action on $Ca^{2+}$ movement, which may account, at least in part, for relaxing action of rat trachealis. trachealis.

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Analysis of gamma-ray-induced DNA damage in human, mouse and rat peripheral blood lymphocytes using single-cell gel electrophoresis (단세포 전기영동법을 이용한 인체, 마우스 및 랫드 림프구의 방사선에 의해 유발된 DNA 손상 측정)

  • Oh, Heon;Jung, Uhee;Park, Hae-Ran;Kim, Sung-Ho;Jo, Sung-Kee
    • Korean Journal of Veterinary Research
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    • v.44 no.1
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    • pp.41-47
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    • 2004
  • The alkaline single-cell gel electrophoresis (SCGE) assay, called the comet assay, has been applied to detect DNA damage induced by a number of chemicals and biological factors in vivo and in vitro. The DNA damage was analysed by tail moment (TM) and tail length (TL), which were markers of DNA strand breaks in SCGE. Human, mouse and rat peripheral blood lymphocytes (PBLs) were irradiated with different doses of $^{60}Co$ ${\gamma}$-rays, e.g. 1, 2, 4, and 8 Gy at a dose rate of 1 Gy/min. A dose-dependent increase in TM (p<0.01) and TL (p<0.01) was obtained at all the radiation doses (1-8 Gy) in human, mouse and rat PBLs. Mouse PBLs were more sensitive than human PBLs which were in turn more sensitive than rat PBLs when the treated dosages were 1 and 2 Gy. However, human PBLs were more sensitive than mouse PBLs which were in turn more sensitive than rat PBLs when the irradiation dosages were 4 and 8 Gy. Data from all three species could be fitted to a linear-quadratic model. These results indicated that there may be inherent differences in the radio-sensitivity among PBLs of mammalian species.