• Title/Summary/Keyword: Monocrotaline

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Effects of Phenoxybenzamine and Propranolol on Monocrotaline Induced Pulmonary Vascular Lesion and Right Ventricular Hypertrophy (Phenoxybenzamine 과 Propranolol 이 Monocrotaline 에 의한 백서 폐동맥 및 우심실벽의 비후성 변화에 미치는 효과)

  • 이성광
    • Journal of Chest Surgery
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    • v.19 no.1
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    • pp.1-11
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    • 1986
  • Using an experimental model of pulmonary hypertension, the effects of anticonstrictive drugs on the development of pulmonary vascular remodeling and right ventricular hypertrophy were studied. Male Sprague-Dawley rats weighing 200~250 gm were used. For the experimental model of pulmonary hypertension, a group of animal was given by a subcutaneous injection of monocrotaline on a dose of 20mg, 40mg, or 60mg per kg of body weight. After 4 weeks of injection, all animals were sacrificed. Another group of animal was given by a subcutaneous injection of monocrotaline in a dose of 40 mg per kg of body weight. The animals were sacrificed, in which they were kept alive for 1, 2, 3 and 4 weeks, respectively. For the effects of anticonstrictive drugs on the development of pulmonary vascular remodeling and right ventricular hypertrophy, the animals treated with monocrotaline were given daily by an intraperitoneal injection of phenoxybenzamine in a dose of 1.3mg/kg of body weight, and were given propranolol via their drinking water at a concentration of 400mg/liter. The animals were sacrificed after 4 weeks of administration. The hearts and lungs were examined histopathologically and morphometrically. The results obtained were summarized as follows: 1. The rats treated with monocrotaline showed an interstitial pneumonitis, medial thickening of the pulmonary small arteries and hypertrophy of the right ventricular wall. 2. The medial thickening of the pulmonary arteries in rats treated with monocrotaline was due to muscular hypertrophy and hyperplasia, and the right ventricular hypertrophy was due to hypertrophy of cardiac muscles. Both medial thickening of the pulmonary arteries and hypertrophy of right ventricular wall were more marked with time and with dose. 3. The daily intraperitoneal injection of phenoxybenzamine suppressed significantly the percentage medial thickness of pulmonary small arteries and the index of right ventricular hypertrophy in rats given a single subcutaneous injection of monocrotaline, but propranolol has shown no protective effect on the development of medial thickening of pulmonary arteries and right ventricular hypertrophy in treated with monocrotaline. The results described above suggested that monocrotaline is an alkaloid selectively inducing pulmonary hypertension and that a-adrenergic receptor is responsible for the pathogenesis of monocrotaline induced pulmonary hypertension in rat.

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The Effects of Jibeakjihwanghwangami(JJHG) on Monocrotaline-induced Hypertensive Rats (지백지황환가미(知柏地黃丸加味)가 monocrotaline으로 유발된 흰쥐의 고혈압 병태모델에 미치는 영향)

  • Kim, Jong-Won;An, Joung-Jo;Jo, Hyun-Kyung;Yoo, Ho-Ryong;Seol, In-Chan;Kim, Yoon-Sik
    • The Journal of Internal Korean Medicine
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    • v.29 no.3
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    • pp.684-702
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    • 2008
  • This experiment was performed to determine the effect of Jibeakjihwanghwangami(JJHG) on hypertension in monocrotaline-induced hypertensive rats. The results obtained were as follows : 1. JJHG showed a safety in cytotoxicity and toxicity of liver. 2. JJHG showed scavenging activity on DPPH free radicals and SOD-like activity. 3. JJHG showed an inhibitory effect on ACE. 4. JJHG significantly decreased blood pressure and pulse in monocrotaline-induced hypertensive rats. 5. JJHG significantly decreased the levels of plasma aldosterone in monocrotaline-induced hypertensive rats. 6. JJHG significantly decreased the levels of potassium in monocrotaline-induced hypertensive rats. 7. JJHG significantly decreased the levels of uric acid. BUN, and creatinine in monocrotaline-induced hypertensive rats. These results suggest that JJHG might be effective in treatment and prevention of hypertension.

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Scanning Electron Microscopic Observation on Early Vascular Lesion in Rat Lung Administered with Monocrotaline (Monocrotaline을 투여한 백서 폐의 초기 혈관병변에 관한 주사전자현미경적 관찰)

  • Park, In-Ae;Ham, Eui-Keun
    • Applied Microscopy
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    • v.21 no.1
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    • pp.86-107
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    • 1991
  • An experimental study was performed to observe the early effects of monocrotaline on pulmonary vascular system by means of light microscopy and scanning electron microscopy, attempting to expore the mechanism behind the process of pulmonary hypertension. Experimental animal(Sprague-Dawley male rats ; 150-200g B. W.) were intra-peritoneal administered with 100mg/kg B. W. monocrotaline. Authors observed light microscopically various gradational increase of wall thickness in pulmonary muscular and non-muscular arteries in duration from 2 weeks to 5 weeks after monocrotaline administration and the changes were more sever in the latter than the former. The scanning electron microscopy shows severe and diffuse endothelical cell swelling, microvilli and microbleb formation since 1 hour after monocrotaline administration and during the course, after 5 hours the severity of endothelial cell damage was prominent with presence of fibrin, webs, platelet thrombi and white cell adherence. It was concluded that the monocrotaline primarily induced severe and diffuse endothelial cell damage of pulmonary arteries and laterly added the participation of platelets, which attributed to the pathogenesis of monocrotaline induced pulmonary vascular lesions in relation to pulmonary hypertension.

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An inhibitory effect of tumor necrosis factor-alpha antagonist to gene expression in monocrotaline-induced pulmonary hypertensive rats model

  • Kwon, Jung Hyun;Kim, Kwan Chang;Cho, Min-Sun;Kim, Hae Soon;Sohn, Sejung;Hong, Young Mi
    • Clinical and Experimental Pediatrics
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    • v.56 no.3
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    • pp.116-124
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    • 2013
  • Purpose: Tumor necrosis factor (TNF)-${\alpha}$ is thought to contribute to pulmonary hypertension. We aimed to investigate the effect of infliximab (TNF-${\alpha}$ antagonist) treatment on pathologic findings and gene expression in a monocrotaline-induced pulmonary hypertension rat model. Methods: Six-week-old male Sprague-Dawley rats were allocated to 3 groups: control (C), single subcutaneous injection of normal saline (0.1 mL/kg); monocrotaline (M), single subcutaneous injection of monocrotaline (60 mg/kg); and monocrotaline + infliximab (M+I), single subcutaneous injection of monocrotaline plus single subcutaneous injection of infliximab (5 mg/kg). The rats were sacrificed after 1, 5, 7, 14, or 28 days. We examined changes in pathology and gene expression levels of TNF-${\alpha}$, endothelin-1 (ET-1), endothelin receptor A (ERA), endothelial nitric oxide synthase (eNOS), matrix metalloproteinase (MMP) 2, and tissue inhibitor of matrix metalloproteinase (TIMP). Results: The increase in medial wall thickness of the pulmonary arteriole in the M+I group was significantly lower than that in the M group on day 7 after infliximab treatment (P<0.05). The number of intraacinar muscular arteries in the M+I group was lower than that in the M group on days 14 and 28 (P<0.05). Expression levels of TNF-${\alpha}$, ET-1, ERA, and MMP2 were significantly lower in the M+I group than in the M group on day 5, whereas eNOS and TIMP expressions were late in the M group (day 28). Conclusion: Infliximab administration induced early changes in pathological findings and expression levels of TNF-${\alpha}$, and MMP2 in a monocrotaline-induced pulmonary hypertension rat model.

Effect of Hyeonsamdansameum on Hypertensive Rat Induced Monocrotaline (현삼단삼음(玄蔘丹蔘飮)이 Monocrotaline으로 유발된 고혈압 흰쥐에 미치는 영향)

  • Kang, Cheol-Sik;Jeon, Sang-Yun;Hong, Seok
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.5
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    • pp.1223-1235
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    • 2008
  • This experiment was performed to investigate the effects of Hyeonsamdansameum(HDE) on hypertension. For the study of HDE, we had divided Sprague-Dawley rats to three groups-normal, control, HDE. The control group was injected subcutaneous with monocrotaline(50 mg/kg). The treatment group was injected subcutaneous with monocrotaline(50 mg/kg) and orally administered with HDE extract for 4 weeks(once a day, 208 mg/kg). Then we measured blood pressure, heart rate, on the plasma aldosterone, catecholamine, electrolyte, uric acid, BUN, creatinine, and observed the lung, cardiac muscle. liver. etc. The results of these were as follows: 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity and superoxide dismutase(SOD) - like activity were increased. reactive oxygen species (ROS) was decreased. Angiotensin converting enzyme(ACE) inhibitory activity was increased in a concentration-dependent by HDE. HDE significantly increased body weight in monocrotaline hypertensive rat, so supported nearly normal group. HDE significantly decreased blood pressure and heart rate in monocrotaline hypertensive rat. HOE significantly decreased aldosterone in adrenocortical hormones. HDE significantly decreased dopamine. norepinephrine, epinephrine. Na+. Cl- were intended to decrease. K+ was decreased significantly by HDE. Uric acid. BUN were significantly decreased and creatinine was intended to decrease by HDE. HDE inhibited lung, liver and heart injury connected with hypertension. These results suggest that HDE is usefully applied in treatment and prevention of hypertension.

Effect of endothelin receptor blockade on monocrotaline-induced pulmonary hypertension in rats (Monocrotaline으로 유발한 백서 폐동맥 고혈압에서 Endothelin 수용체 차단제 투여의 효과)

  • Lim, Kyoung Ah;Shim, Jung Yun;Cho, Sang Ho;Kim, Kwan Chang;Han, Jae Jin;Hong, Young Mi
    • Clinical and Experimental Pediatrics
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    • v.52 no.6
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    • pp.689-695
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    • 2009
  • Purpose : To examine the effect of bosentan, a dual endothelin receptor (ER) antagonist, on the development of monocrotaline (MCT)-induced pulmonary hypertension in rats by especially focusing on the pulmonary vascular morphology changes. Methods : Sprague-Dawley rats were treated as follows: controls received a subcutaneous saline injection, MCT-treated rats received a subcutaneous MCT injection, and bosentan-treated rats received a MCT injection followed by treatment with bosentan (20 mg/kg/day). To assess the effects of ER blockade on the time course, the animals were exsanguinated, and their hearts and lungs were dissected after 7, 14, or 28 days. Results : The mean body weights of the MCT- and bosentan-treated rats were significantly lower than that of the control rats on days 7, 14, and 28. Bosentan administration significantly inhibited the progression of right ventricular hypertrophy on day 28 (right ventricle/[left ventricle+septum]: $0.71{\pm}0.10$ in MCT-treated rats vs. $0.49{\pm}0.09$ in bosentan-treated rats; P<0.05). Quantitative analysis of peripheral pulmonary arteries revealed that the increase in medial wall thickness after MCT injection was significantly attenuated in the bosentan-treated rats on day 28 ($49.96{\pm}10.06%$ in MCT-treated rats vs. $47.09{\pm}10.48%$ in bosentan-treated rats; P<0.05). In addition, the increase in the number of intra-acinar muscular arteries after MCT injection was reduced by bosentan on days 14 and 28. Conclusion : Bosentan administration in intermediate doses exerts inhibitory effects on lung vascular hypertrophy and right ventricular hypertrophy during the development of MCT-induced pulmonary hypertension in rats.

Inhibitory Effect of Enalapril in Combination with Ginkgo biloba Extract (EGb 761) on the Monocrotaline-induced Pulmonary Hypertension Rats (Monocrotaline에 의해 유발된 폐고혈압 흰쥐에 있어 Enalapril 및 Ginkgo biloba Extract(EGb 761)의 병용 투여시 억제효과)

  • 이영미;안형수;임세진;안령미
    • YAKHAK HOEJI
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    • v.43 no.4
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    • pp.487-493
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    • 1999
  • Effects of Ginkgo biloba extract (EGb 761) on the anti-pulmonary hypertensive action of enalapril were evaluated in rats. Pulmonary hypertension was induced by monocrotaline treatment (60mg/kg, i.p.) in normotensive rats. In the systolic pulmonary artery pressure, the control group was 33$\pm$2 mmHg, comparing to the normal group of 19$\pm$1 mmHg. That of enalapril group(20mg/kg/day, p.o.) was 26$\pm$2 mmHg. In the isolated lung preparation, acetylcholine, which was endothelium dependent vasodilator, induced the decrease of pulmonary artery perfusion pressure(-2.0$\pm$0.7 mmHg) in normal group, but the increase of that of 3.4$\pm$0.6 and 3.0$\pm$0.9 mmHg in control and enalapril group, respectively. And that of the combined group was -0.5$\pm$0.2 mmHg. In the isolated pulmonary artery, acetylcholine(10-5M) induced the relaxation of 65$\pm$6% in normal group, but 15 and 8% in control and enalapril group, respectively. And that of the combined group was resulted 55$\pm$2%. These results suggested that co-administration of Ginkgo biloba extract(EGb 761) potentiated the anti-pulmonary hypertensive effects of enalapril through the increase of pulmonary vasodilation due to the protection of endothelial cell by antioxidant action of Ginkgo biloba extract (EGb 761).

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DA-8159, a Potent cGMP Phosphodiesterase Inhibitor, Attenuates Monocrotaline-Induced Pulmonary Hypertension in Rats

  • Kang, Kyung-Koo;Ahn, Gook-Jun;Sohn, Yong-Sung;Ahn, Byoung-Ok;Kim, Won-Bae
    • Archives of Pharmacal Research
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    • v.26 no.8
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    • pp.612-619
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    • 2003
  • In this study, we evaluated the effects of oral administration of DA-8159, a selective phosphodiesterase-5 inhibitor, on the development of pulmonary hypertension (PH) induced by monocrotaline (MCT). Rats were administered either MCT (60 mg/kg) or saline. MCT-treated rats were divided into three groups and received orally administered vehicle, or 1 mg/kg or 5 mg/kg of DA-8159, twice a day for twenty-one days. The MCT group demonstrated increased right ventricular weights, medial wall thickening in the pulmonary arteries, myocardial fibrosis and the level of plasma cyclic guanosine monophosphate (cGMP), along with decreased body weight gains. However, DA-8159 markedly and dose-dependently reduced the development of right ventricular hypertrophy and medial wall thickening. DA-8159 also amplified the increase in plasma cGMP level and significantly increased the level of lung cGMP, compared with the MCT group. Although the body weight gain was still lower from the saline-treated control group, DA-8159 demonstrated a significant increase in body weight gains, in both 1 mg/kg and 5 mg/kg groups, when compared with the MCT group. In myocardial morphology, MCT-induced myocardial fibrosis was markedly prevented by DA-8159. These results suggest that DA-8159 may be a useful oral treatment option for PH.

Attenuation of monocrotaline-induced pulmonary hypertension with DA-8159, a potent PDE 5 inhibitor

  • Ahn, Gook-Jun;Kang, Kyung-Koo;Sohn, Yong-Sung;Choi, Seu-Min;Kim, Ju-Mi;Kim, Dong-Hwan;Ahn, Byoung-Ok;Kim, Won-Bae
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.249.1-249.1
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    • 2002
  • This study was carried out to demonstrate the effects of oral administration of DA-8159. a selective phosphodiesterase 5 inhibitor. on development of pulmonary hypertension induced by monocrotaline (MCT). MCT-treated rats(60mg/kg) were divided into three groups and orally administered vehicle, 1 mg/kg or 5 mg/kgg of DA-8159 twice a day for 3 weeks. Increased right ventricular weights, medial wall thickening in pulmonary arteries. myocardial fibrosis, decrease of plasma cyclic guanosine monophosphate (cGMP) level and body weight gains were shown in MCT group. (omitted)

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