- Email: [email protected]
P132 Salvia miltiorrhiza inhibits neointimal hyperplasia following balloon injury in cholesterol-fed rabbits
S81
Poster Abstracts
P132
P130
Hemodynamic effect on the oxidant generation H~yue-Jen H&h*. Chia-Chen Cheng*, Shing-Ta Wung + and Danny L. Wang +
in cultured endothelial cells Wu*, Jeng-Jiami Chiu +, Being-Sun
*Department of Chemical Engineering, National Taiwan University, and ‘Institute of 13iomedical Sciences, Academia Sinica, Taipei. Tawan
Many clinical reports point out that most of the atherosclerotic lesions occur in the vascular tree at regions with disturbed patterns of blood flow, indicating that hemodynamic forces play an important role in the development of atherosclerosis. Vascular endothehal cells line the blood vessels and contact directly with the blood flow-generated shear forces. Recent studies indicate that excessive oxidant generation is involved in the atherogenesis. Moderate elevation of intracellular oxidant levels, however, may function as potential intracellular signaling molecules. Regulation of intracellular oxidative state by oxidant generation and cellular antioxidant activity thus plays an important role in cellular physiology as well as pathology. In this study, an in vitro flow system constituted by a parallel-plate flow chamber and a circulation loop was utilized to study the effect of shear flow on cultured human umbilical vein endothehal cells (ECs). The exertion of shear flow resulted in a significant generatIon of oxidant in ECs. Further experiments revealed that oxidant species possibly involved were hydrogen peroxide. hydroxyl radical, etc. In the mean time, the cellular antioxidant activity was also enhanced by shear flow. The significance of flow- induced oxidant generation was further investigated by examining its role in gene expression. It was found that the oxidant generation was involved in the signaling pathway which led to the expression of several genes including proto-oncogene c-fos. This study demonstrates that oxidant generation plays an important role in the regulation of intracellular events in ECs subjected to hemodynamic shear flow. (Supported by the National Science Council, R.O.C. grants: NSC85-2331.B-002.138.M26 and NSC86.2314-B-002.041.MZ6).
SALl44 MILTlORRHIZ4 INHIBITS NEOINTIMAL LOWING BALLOON INJURY IN CAOLESTEROGFED Sung-Pm Yang, Yuh-Lien Chen, Li-Ling Chou, Ming-Shi Shing-Jong Lm
HYPERPLASIA RABBITS Shiao, Chuang-Ye
FOLHong,
Veterans General Hospital-Taipei; National Yang-Mmg Unwersity, Taiwan
Objective: Neomtnnal hyperplasia is often responsible for restenotic lesions after halloon angioplasty. &/da mihiorrhiza (Damhen) is a Chinese medicinal herb widely used for treatment of atherosclerosis-related disorders. The effects of water-soluble antioxidant-rich fraction of Danshen on intimal response to balloon injury of aorta were studied in cholesterol-fed rabbits. Methods: Male New Zealand white rabbits were fed with 2% cholesterol diet together with 3 gm/kg B.W./day Danshen crude extract (treatment group: n = 9) or without Danshen (control group; n = 8) for a total of 6 weeks. A balloon injury of abdominal aorta was performed at the end of third week. The animals were sacrificed and abdominal aortas were harvested at the end of 6 weeks of treatment. Neointimal hyperplasia in aorta was determined morphometrically. Results: The Danshen-treated rabbits had significantly less neointimal hyperplasia than those of control group (intima thickness: 156.0 * 10.2 vs 197.2 * 11.6 pm: P < 0.05; intima/media thickness ratio: 0.80 * 0.05 vs 1.04 k 0.06, P < 0.01). No difference in serum biochemistry was found. Conclusions: Water-soluble antioxidant-rich fractmn of Salaa mihiorrhiza significantly reduced neointimal hyperplasia following balloon injury in cholesterol-fed rabbits. These effects might be attributed to its antioxidant capacity rather than lowering serum cholesterol. These findings might have clinical implication in the prevention of post-angioplasty restenosis.
P133 P131 The effects of hypertension expression in rats Tz-Chong Chou, Mao-Hsiung Cardioprotective action of melatonia in rats Mao-Hsiwg Yen, Huey-Rue Chen
in myocardial
ischemia/reperfusion
injury
Tri-Serwe
and
quiospril
Yen, Yu-An
treatment
on nitric
oxide
synthase
Ding
General Hospital, Taipei, Taiwan
National Defense MedIcal Center, T.lipei, Taiwan
Objective: This study was undertaken to evaluate the cardioprotective activny of melatonin in myocardiai ischemia/reperfusion injury. Methods: Myocardial ischemia/reperfusion was induced by 45 mm occlusion of the left coronary artery followed by 1 h repafusion. Anesthetized Sprague-Dawley rats (either sex; 250-300 g) were used and randomly assigned to one of four treatment groups: control, m&ronin 0.5, 1.0 and 5.0 mg/kg, which were administered (iv bolus) 10 mm prior to occlusion. Results: Results demonstrated that the intermediate and high doses of melatonin (1.0 and 5 0 mg/kg) markedly delayed the onset of arrhythmias and significantly suppressed the incidence of ventricular tachycardia (VT) and ventricular tibrillation (VP), with reducing the total number of ventrxular premature contractions (VP0 and total duration of VT aId VP occurred during ischemic period. A significant reduction of mortality of rats was observed in all melatonin-treatment groups. After reperfusion, melatonin caused a significant reduction in infarct size when compared with controls (melasmin - 0.5 mg/kg: 37.5.0 i 2.3% melatonin 1.0 mg/kg: 24.8 & 2.68, melatonin -- 5.0 mg/kg: 28.2 f 2.8% vs control: 58.8 + 3.0%). Meanwhile, melatonin (1.0 mg/kg) suppressed the activity of myeloperoxidase, an index of neutrophils intiltratmn in the ischemic myocardium, as compared with the value of control group. Conclusions: It is concluded that melatonin can suppress &hernia-induced ventricular arrhythmias and reduce the infarct size and cardiac myeloperoxidase activity resulting from ischemia/reperfusion injury. The pronounced cardioprotective activity of melatonin offers a new and effective therapeutic approach to ischemic coronary diseases.
Objectwe: The aims of this study was to (I) investigate whether the activity and protein expression of eNOS and iNOS are changed during the development of hypertension in SHR, (II) to evaluate the effects of quinapril treatment on the changes of NOS expression in SHR. Methods: NOS activity and protein expression ot aorta were determined by [3H]L-citrulline formation and western blot analysis, respectively, at three age groups: 4, 14-17 and 63.weeks old. Results: At 14-17 and 63 weeks, the basal activity and protein expression of eNOS in the aorta were significantly lower in SHR than in WKY. In addition, the aged WKY has lower eNOS activity compared with that of adult WKY. The basal or lipopolysaccharide (LPS) induced- activity and protein expression of iNOS in SHR of 14-17 and 63-weeks group were significantly higher than that of WKY. Furthermore, the basal and LPS-induced NO, - /NO, - and TN&x levels in the plasma were also higher in SHR. After treatment with quinapril for two weeks, .the basal and LPS-induced expression of iNOS in SHR were significantly attenuated. Conclusions: The alterations of eNOS and iNOS occurred in SHR. The decline of eNOS may contribute to the development of hypertension, whereas, the increase of iNOS may be a consequence of pathological state of vessels associated with hypertension. Antihypertensive treatment with ACEI, quinapril, could attenuate the abnormal expression of INOS, which may be a beneficial effect on hypertension.
Poster Abstracts
P132
P130
Hemodynamic effect on the oxidant generation H~yue-Jen H&h*. Chia-Chen Cheng*, Shing-Ta Wung + and Danny L. Wang +
in cultured endothelial cells Wu*, Jeng-Jiami Chiu +, Being-Sun
*Department of Chemical Engineering, National Taiwan University, and ‘Institute of 13iomedical Sciences, Academia Sinica, Taipei. Tawan
Many clinical reports point out that most of the atherosclerotic lesions occur in the vascular tree at regions with disturbed patterns of blood flow, indicating that hemodynamic forces play an important role in the development of atherosclerosis. Vascular endothehal cells line the blood vessels and contact directly with the blood flow-generated shear forces. Recent studies indicate that excessive oxidant generation is involved in the atherogenesis. Moderate elevation of intracellular oxidant levels, however, may function as potential intracellular signaling molecules. Regulation of intracellular oxidative state by oxidant generation and cellular antioxidant activity thus plays an important role in cellular physiology as well as pathology. In this study, an in vitro flow system constituted by a parallel-plate flow chamber and a circulation loop was utilized to study the effect of shear flow on cultured human umbilical vein endothehal cells (ECs). The exertion of shear flow resulted in a significant generatIon of oxidant in ECs. Further experiments revealed that oxidant species possibly involved were hydrogen peroxide. hydroxyl radical, etc. In the mean time, the cellular antioxidant activity was also enhanced by shear flow. The significance of flow- induced oxidant generation was further investigated by examining its role in gene expression. It was found that the oxidant generation was involved in the signaling pathway which led to the expression of several genes including proto-oncogene c-fos. This study demonstrates that oxidant generation plays an important role in the regulation of intracellular events in ECs subjected to hemodynamic shear flow. (Supported by the National Science Council, R.O.C. grants: NSC85-2331.B-002.138.M26 and NSC86.2314-B-002.041.MZ6).
SALl44 MILTlORRHIZ4 INHIBITS NEOINTIMAL LOWING BALLOON INJURY IN CAOLESTEROGFED Sung-Pm Yang, Yuh-Lien Chen, Li-Ling Chou, Ming-Shi Shing-Jong Lm
HYPERPLASIA RABBITS Shiao, Chuang-Ye
FOLHong,
Veterans General Hospital-Taipei; National Yang-Mmg Unwersity, Taiwan
Objective: Neomtnnal hyperplasia is often responsible for restenotic lesions after halloon angioplasty. &/da mihiorrhiza (Damhen) is a Chinese medicinal herb widely used for treatment of atherosclerosis-related disorders. The effects of water-soluble antioxidant-rich fraction of Danshen on intimal response to balloon injury of aorta were studied in cholesterol-fed rabbits. Methods: Male New Zealand white rabbits were fed with 2% cholesterol diet together with 3 gm/kg B.W./day Danshen crude extract (treatment group: n = 9) or without Danshen (control group; n = 8) for a total of 6 weeks. A balloon injury of abdominal aorta was performed at the end of third week. The animals were sacrificed and abdominal aortas were harvested at the end of 6 weeks of treatment. Neointimal hyperplasia in aorta was determined morphometrically. Results: The Danshen-treated rabbits had significantly less neointimal hyperplasia than those of control group (intima thickness: 156.0 * 10.2 vs 197.2 * 11.6 pm: P < 0.05; intima/media thickness ratio: 0.80 * 0.05 vs 1.04 k 0.06, P < 0.01). No difference in serum biochemistry was found. Conclusions: Water-soluble antioxidant-rich fractmn of Salaa mihiorrhiza significantly reduced neointimal hyperplasia following balloon injury in cholesterol-fed rabbits. These effects might be attributed to its antioxidant capacity rather than lowering serum cholesterol. These findings might have clinical implication in the prevention of post-angioplasty restenosis.
P133 P131 The effects of hypertension expression in rats Tz-Chong Chou, Mao-Hsiung Cardioprotective action of melatonia in rats Mao-Hsiwg Yen, Huey-Rue Chen
in myocardial
ischemia/reperfusion
injury
Tri-Serwe
and
quiospril
Yen, Yu-An
treatment
on nitric
oxide
synthase
Ding
General Hospital, Taipei, Taiwan
National Defense MedIcal Center, T.lipei, Taiwan
Objective: This study was undertaken to evaluate the cardioprotective activny of melatonin in myocardiai ischemia/reperfusion injury. Methods: Myocardial ischemia/reperfusion was induced by 45 mm occlusion of the left coronary artery followed by 1 h repafusion. Anesthetized Sprague-Dawley rats (either sex; 250-300 g) were used and randomly assigned to one of four treatment groups: control, m&ronin 0.5, 1.0 and 5.0 mg/kg, which were administered (iv bolus) 10 mm prior to occlusion. Results: Results demonstrated that the intermediate and high doses of melatonin (1.0 and 5 0 mg/kg) markedly delayed the onset of arrhythmias and significantly suppressed the incidence of ventricular tachycardia (VT) and ventricular tibrillation (VP), with reducing the total number of ventrxular premature contractions (VP0 and total duration of VT aId VP occurred during ischemic period. A significant reduction of mortality of rats was observed in all melatonin-treatment groups. After reperfusion, melatonin caused a significant reduction in infarct size when compared with controls (melasmin - 0.5 mg/kg: 37.5.0 i 2.3% melatonin 1.0 mg/kg: 24.8 & 2.68, melatonin -- 5.0 mg/kg: 28.2 f 2.8% vs control: 58.8 + 3.0%). Meanwhile, melatonin (1.0 mg/kg) suppressed the activity of myeloperoxidase, an index of neutrophils intiltratmn in the ischemic myocardium, as compared with the value of control group. Conclusions: It is concluded that melatonin can suppress &hernia-induced ventricular arrhythmias and reduce the infarct size and cardiac myeloperoxidase activity resulting from ischemia/reperfusion injury. The pronounced cardioprotective activity of melatonin offers a new and effective therapeutic approach to ischemic coronary diseases.
Objectwe: The aims of this study was to (I) investigate whether the activity and protein expression of eNOS and iNOS are changed during the development of hypertension in SHR, (II) to evaluate the effects of quinapril treatment on the changes of NOS expression in SHR. Methods: NOS activity and protein expression ot aorta were determined by [3H]L-citrulline formation and western blot analysis, respectively, at three age groups: 4, 14-17 and 63.weeks old. Results: At 14-17 and 63 weeks, the basal activity and protein expression of eNOS in the aorta were significantly lower in SHR than in WKY. In addition, the aged WKY has lower eNOS activity compared with that of adult WKY. The basal or lipopolysaccharide (LPS) induced- activity and protein expression of iNOS in SHR of 14-17 and 63-weeks group were significantly higher than that of WKY. Furthermore, the basal and LPS-induced NO, - /NO, - and TN&x levels in the plasma were also higher in SHR. After treatment with quinapril for two weeks, .the basal and LPS-induced expression of iNOS in SHR were significantly attenuated. Conclusions: The alterations of eNOS and iNOS occurred in SHR. The decline of eNOS may contribute to the development of hypertension, whereas, the increase of iNOS may be a consequence of pathological state of vessels associated with hypertension. Antihypertensive treatment with ACEI, quinapril, could attenuate the abnormal expression of INOS, which may be a beneficial effect on hypertension.