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. 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 AngII level may be associated with the decrease of ACE activity.