Background Congestive heart failure (CHF) is a major cause of morbidity and mortality worldwide and angiotensin convertingenzyme inhibitor (ACEI) is the cornerstone in its treatment However, CHF continues to progress ...Background Congestive heart failure (CHF) is a major cause of morbidity and mortality worldwide and angiotensin convertingenzyme inhibitor (ACEI) is the cornerstone in its treatment However, CHF continues to progress despite this therapy, perhaps because of production of angiotensin Ⅱ (Ang Ⅱ) by alternative pathways The present study was conducted to examine the combined effects of a chronic ACEI, ramipril, and a chronic Ang Ⅱ type 1 receptor blocker, TCV116, on rat CHF after myocardial infarction (MI) Methods Congestive heart failure was caused by MI in rats, which was induced by ligating the left anterior descending coronary artery The experiment protocol included shamoperated rats (Sham), MIcontrol rats (MIcontrol), MI rats treated with ramipril 3 mg/kg (MIramipril) or TCV116 2 mg/kg (MITCV116) per day, half dosage (MI1/2R&T) or full dosage (MIR&T) combination of the two At 22 weeks, cardiac hemodynamic parameters such as mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), maximal rate of left ventricule pressure development and decline (LV dP/dtmax) and left ventricular end diastolic pressure (LVEDP), and cardiac morphometric parameters such as heart weight (HW), left ventricular weight (LVW) and left ventricular cavity area (LVCA) were measured, mRNA expressions of cardiac molecule genes such as β myosin heavy chain (βMHC), Btype natriuretic peptide (BNP), transforming growth factorβ1 (TGFβ1), collagen I and Ⅲ were quantified with reverse transcription polymerase chain reaction (RTPCR) in the surviving septum myocardium, and survival rates were calculated Results There were no significant differences in MI sizes (%) among each MI related experimental groups (33±13, 34±14, 33±13, 35±13 and 33±14 for MIcontrol, MIramipril, MITCV116, MI1/2R&T and MIR&T, respectively, no statistical significance for all) Compared with shamoperated rats, MI rats without therapy showed significant increases in morphometric parameters as well as in mRNA expressions of cardiac molecule genes (P<001); while their hemodynamic parameters were significantly impaired (P<001), and in terms of spontaneous deaths survival rate shortened (P<005) Compared with MI rats without therapy, MI rats treated with each single drug showed significant attenuation of mRNA expressions of cardiac molecule genes (P<001); while their hemodynamic parameters were significantly improved (P<005 or P<001), and in terms of spontaneous deaths survival rate prolonged (P<005) Both half and full dosage combined treatments exerted more powerful effects on improvement of cardiac phenotypic changes and on attenuation of βMHC, BNP mRNA expressions (P<005 vs monotherapy); while LVEDP was further lowered (P<005 vs monotherapy) However, the total death in MI rats with full dosage combined treatment was more though there were no significant differences when compared with other treatmentsConclusions The results suggest that treatment with appropriate dosage combination of a chronic ACEI and a chronic ARB may further improve cardiac remodeling and cardiac function after MI展开更多
Background Little is known about the role of dual angiotensin Ⅱ forming pathways during heart failure. In the present study, the changes of chymase and angiotensin converting enzyme （ACE） expressions in the failing...Background Little is known about the role of dual angiotensin Ⅱ forming pathways during heart failure. In the present study, the changes of chymase and angiotensin converting enzyme （ACE） expressions in the failing hearts of hamsters were analysed. Methods Heart failure was induced by ligation of left anterior descending branch of the coronary artery. Chymase, ACE and angiotensin Ⅱ type 1 receptor （AT1R） mRNA levels were analysed by reverse transcription polymerase chain reaction （RT-PCR）. The activities of chymase and ACE were determined by radioimmunoassay （RIA）. Myocardial collagen fibre analysis was performed under optical microscope. Results Left ventricular systolic pressure （LVSP） and maximum left ventricular developed pressure increase rate （ dp/dtmax, mmHg/s） gradually moved lower at 2, 3,4 and 8 weeks after operation. On the other hand, left ventricular end-diastolic pressure （LVEDP） increased gradually after operation. Compared with the control group （3.55±0. 06, 4.79±0.70）, the heart weight/body weight ratio in operation group had increased significantly at 4 weeks and 8 weeks （4. 28±0. 43, 6. 17±0.73） （P 〈0. 01 ）. Collagen staining showed that the quantity of myocardial collagen fibre increased significantly in the operation group. RT-PCR showed that the chymase mRNA level in the operation group was consistently greater than that in the control group. ATIR mRNA level was also increased significantly at 3 weeks and 4 weeks, both being 1.3 times that of the control group （ P〈0.01 ）, whereas ACE mRNA level was not changed. Higher activity of chymase was detected in operation group, being 4, 8, 13 and 19 times that of the control group at 2, 3, 4 and 8 weeks （P〈0.01 ）, respectively. ACE activity was also significantly higher at the same time, being 7, 10, 10 and 3.5 times that of the control（P〈0.01）. Angiotensin Ⅱ （Ang Ⅱ） level in operation group increased significantly, being 2.5, 2.7, 3.5 and 2 times that of the control group at 2, 3, 4 and 8 weeks, respectively （P 〈 0. 01 ）. Conclusions A dual Ang Ⅱ forming pathway from both ACE and chymase in the hamster hearts plays an important role during the development of heart failure. At the decompensatory stage, the reduction of AngⅡ level may be associated with the decrease of ACE activity.展开更多
Chronic heart failure （CHF）, as the end-stage presentation of all kinds of heart diseases, is a major public health problem as well issue. There are more than 5 as a pressing public policy million patients diagnosed...Chronic heart failure （CHF）, as the end-stage presentation of all kinds of heart diseases, is a major public health problem as well issue. There are more than 5 as a pressing public policy million patients diagnosed with CHF in USA alone and approximately 550 000 new cases appear per year. About 0.4%-2% of the European population is affected by symptomatic heart failure. Hence heart failure is the leading cause of hospitalization especially in older people around the world.展开更多
目的:探讨三七总皂苷对慢性心力衰竭大鼠心脏功能、血浆利钠肽及血管紧张素Ⅱ的影响。方法:将60只健康雄性清洁级Wistar大鼠随机分为4组,即对照组、模型组、三七总皂苷低剂量组和三七总皂苷高剂量组,每组15只。除对照组外,其余3组均建...目的:探讨三七总皂苷对慢性心力衰竭大鼠心脏功能、血浆利钠肽及血管紧张素Ⅱ的影响。方法:将60只健康雄性清洁级Wistar大鼠随机分为4组,即对照组、模型组、三七总皂苷低剂量组和三七总皂苷高剂量组,每组15只。除对照组外,其余3组均建立慢性心力衰竭大鼠模型。对三七总皂苷低剂量组和三七总皂苷高剂量组大鼠分别给予51、105 mg·kg -1 剂量的三七总皂苷治疗。检测各组大鼠平均动脉压(mean arterial pressure,MAP)、左心室收缩压(left ventricular systolic pressure,LVSP)、左心室压最大上升速率(maximal rate of the increase of left ventricular pressure,+dp/dt)、左心室压最大下降速率(maximal rate of the decrease of left ventricular pressure,- dp/dt),以及大鼠血清和心肌组织中利钠肽、血管紧张素Ⅱ水平。结果:与对照组比较,模型组、三七总皂苷低剂量组、三七总皂苷高剂量组大鼠MAP、LVSP水平,+dp/dt、- dp/dt数值均明显降低,利钠肽、血管紧张素Ⅱ水平均明显升高,差异均有统计学意义(均 P <0.05)。与模型组比较,三七总皂苷低剂量组、三七总皂苷高剂量组大鼠MAP、LVSP水平,+dp/dt、- dp/dt数值均明显升高,利钠肽及血管紧张素Ⅱ水平均明显降低,且高剂量组变化趋势更明显,差异均有统计学意义(均 P <0.05)。模型组心肌细胞排列紊乱,心肌纤维呈波浪形,部分断裂;三七总皂苷低、高剂量组大鼠心肌细胞排列较整齐,边缘清楚,无肌纤维断裂,胞浆纹理清晰。结论:三七总皂苷可通过调节慢性心力衰竭大鼠心脏功能指标,改善心室收缩肌舒张功能,并降低利钠肽及血管紧张素Ⅱ水平,有效防止心肌重构,对慢性心力衰竭具有一定的治疗效果。展开更多
文摘Background Congestive heart failure (CHF) is a major cause of morbidity and mortality worldwide and angiotensin convertingenzyme inhibitor (ACEI) is the cornerstone in its treatment However, CHF continues to progress despite this therapy, perhaps because of production of angiotensin Ⅱ (Ang Ⅱ) by alternative pathways The present study was conducted to examine the combined effects of a chronic ACEI, ramipril, and a chronic Ang Ⅱ type 1 receptor blocker, TCV116, on rat CHF after myocardial infarction (MI) Methods Congestive heart failure was caused by MI in rats, which was induced by ligating the left anterior descending coronary artery The experiment protocol included shamoperated rats (Sham), MIcontrol rats (MIcontrol), MI rats treated with ramipril 3 mg/kg (MIramipril) or TCV116 2 mg/kg (MITCV116) per day, half dosage (MI1/2R&T) or full dosage (MIR&T) combination of the two At 22 weeks, cardiac hemodynamic parameters such as mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), maximal rate of left ventricule pressure development and decline (LV dP/dtmax) and left ventricular end diastolic pressure (LVEDP), and cardiac morphometric parameters such as heart weight (HW), left ventricular weight (LVW) and left ventricular cavity area (LVCA) were measured, mRNA expressions of cardiac molecule genes such as β myosin heavy chain (βMHC), Btype natriuretic peptide (BNP), transforming growth factorβ1 (TGFβ1), collagen I and Ⅲ were quantified with reverse transcription polymerase chain reaction (RTPCR) in the surviving septum myocardium, and survival rates were calculated Results There were no significant differences in MI sizes (%) among each MI related experimental groups (33±13, 34±14, 33±13, 35±13 and 33±14 for MIcontrol, MIramipril, MITCV116, MI1/2R&T and MIR&T, respectively, no statistical significance for all) Compared with shamoperated rats, MI rats without therapy showed significant increases in morphometric parameters as well as in mRNA expressions of cardiac molecule genes (P<001); while their hemodynamic parameters were significantly impaired (P<001), and in terms of spontaneous deaths survival rate shortened (P<005) Compared with MI rats without therapy, MI rats treated with each single drug showed significant attenuation of mRNA expressions of cardiac molecule genes (P<001); while their hemodynamic parameters were significantly improved (P<005 or P<001), and in terms of spontaneous deaths survival rate prolonged (P<005) Both half and full dosage combined treatments exerted more powerful effects on improvement of cardiac phenotypic changes and on attenuation of βMHC, BNP mRNA expressions (P<005 vs monotherapy); while LVEDP was further lowered (P<005 vs monotherapy) However, the total death in MI rats with full dosage combined treatment was more though there were no significant differences when compared with other treatmentsConclusions The results suggest that treatment with appropriate dosage combination of a chronic ACEI and a chronic ARB may further improve cardiac remodeling and cardiac function after MI
基金This investigation was supported by Major National Basic ResearchProgram, People’s Republic of China (973 Program) (No.G2000056904)
文摘Background Little is known about the role of dual angiotensin Ⅱ forming pathways during heart failure. In the present study, the changes of chymase and angiotensin converting enzyme （ACE） expressions in the failing hearts of hamsters were analysed. Methods Heart failure was induced by ligation of left anterior descending branch of the coronary artery. Chymase, ACE and angiotensin Ⅱ type 1 receptor （AT1R） mRNA levels were analysed by reverse transcription polymerase chain reaction （RT-PCR）. The activities of chymase and ACE were determined by radioimmunoassay （RIA）. Myocardial collagen fibre analysis was performed under optical microscope. Results Left ventricular systolic pressure （LVSP） and maximum left ventricular developed pressure increase rate （ dp/dtmax, mmHg/s） gradually moved lower at 2, 3,4 and 8 weeks after operation. On the other hand, left ventricular end-diastolic pressure （LVEDP） increased gradually after operation. Compared with the control group （3.55±0. 06, 4.79±0.70）, the heart weight/body weight ratio in operation group had increased significantly at 4 weeks and 8 weeks （4. 28±0. 43, 6. 17±0.73） （P 〈0. 01 ）. Collagen staining showed that the quantity of myocardial collagen fibre increased significantly in the operation group. RT-PCR showed that the chymase mRNA level in the operation group was consistently greater than that in the control group. ATIR mRNA level was also increased significantly at 3 weeks and 4 weeks, both being 1.3 times that of the control group （ P〈0.01 ）, whereas ACE mRNA level was not changed. Higher activity of chymase was detected in operation group, being 4, 8, 13 and 19 times that of the control group at 2, 3, 4 and 8 weeks （P〈0.01 ）, respectively. ACE activity was also significantly higher at the same time, being 7, 10, 10 and 3.5 times that of the control（P〈0.01）. Angiotensin Ⅱ （Ang Ⅱ） level in operation group increased significantly, being 2.5, 2.7, 3.5 and 2 times that of the control group at 2, 3, 4 and 8 weeks, respectively （P 〈 0. 01 ）. Conclusions A dual Ang Ⅱ forming pathway from both ACE and chymase in the hamster hearts plays an important role during the development of heart failure. At the decompensatory stage, the reduction of AngⅡ level may be associated with the decrease of ACE activity.
文摘Chronic heart failure （CHF）, as the end-stage presentation of all kinds of heart diseases, is a major public health problem as well issue. There are more than 5 as a pressing public policy million patients diagnosed with CHF in USA alone and approximately 550 000 new cases appear per year. About 0.4%-2% of the European population is affected by symptomatic heart failure. Hence heart failure is the leading cause of hospitalization especially in older people around the world.
文摘目的:探讨三七总皂苷对慢性心力衰竭大鼠心脏功能、血浆利钠肽及血管紧张素Ⅱ的影响。方法:将60只健康雄性清洁级Wistar大鼠随机分为4组,即对照组、模型组、三七总皂苷低剂量组和三七总皂苷高剂量组,每组15只。除对照组外,其余3组均建立慢性心力衰竭大鼠模型。对三七总皂苷低剂量组和三七总皂苷高剂量组大鼠分别给予51、105 mg·kg -1 剂量的三七总皂苷治疗。检测各组大鼠平均动脉压(mean arterial pressure,MAP)、左心室收缩压(left ventricular systolic pressure,LVSP)、左心室压最大上升速率(maximal rate of the increase of left ventricular pressure,+dp/dt)、左心室压最大下降速率(maximal rate of the decrease of left ventricular pressure,- dp/dt),以及大鼠血清和心肌组织中利钠肽、血管紧张素Ⅱ水平。结果:与对照组比较,模型组、三七总皂苷低剂量组、三七总皂苷高剂量组大鼠MAP、LVSP水平,+dp/dt、- dp/dt数值均明显降低,利钠肽、血管紧张素Ⅱ水平均明显升高,差异均有统计学意义(均 P <0.05)。与模型组比较,三七总皂苷低剂量组、三七总皂苷高剂量组大鼠MAP、LVSP水平,+dp/dt、- dp/dt数值均明显升高,利钠肽及血管紧张素Ⅱ水平均明显降低,且高剂量组变化趋势更明显,差异均有统计学意义(均 P <0.05)。模型组心肌细胞排列紊乱,心肌纤维呈波浪形,部分断裂;三七总皂苷低、高剂量组大鼠心肌细胞排列较整齐,边缘清楚,无肌纤维断裂,胞浆纹理清晰。结论:三七总皂苷可通过调节慢性心力衰竭大鼠心脏功能指标,改善心室收缩肌舒张功能,并降低利钠肽及血管紧张素Ⅱ水平,有效防止心肌重构,对慢性心力衰竭具有一定的治疗效果。
