Changes of chymase, angiotensin converting enzyme and angiotensin Ⅱ type 1 receptor expressions in the hamster heart during the development of heart failure

摘要

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/dt_(max) , 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. AT1R 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 Angll level may be associated with the decrease of ACE activity.