Effects of ACE-I on diabetic cardiovascular complications: anti-hypertensive and non-antihypertensive doses.

ABSTRACT

To evaluate the effects of angiotensin converting enzyme inhibitor (ACE-I) on diabetic cardiovascular complications, a streptozotozin (STZ, i.p., 70 mg/kg BW) induced diabetes rat model was used. The animals were separated into four major groups including control (NSS), STZ-treated rats, STZ-treated rats received daily oral feeding of cilazapril starting one day after STZ injection (STZ-C1), and STZ-treated rats received daily oral feeding of cilazapril eight weeks after the STZ injection (STZ-C8). Within the groups of STZ-C1 and STZ-C8, the animals were also divided into three subgroups of six rats that received different doses of cilazapril treatment, 0.01 mg/Kg BW, 1 mg/Kg BW, and 10 mg/Kg BW. By using the modified isolated heart model, the parameters of mean arterial pressure (MAP), heart rate (HR), left ventricular isotonic contraction (LVIC), aortic flow rate (AFR), coronary flow rate (CFR), and ratio of heart weight per body weight (R) were assessed for each groups 8 and 20 weeks after the STZ injections. Moreover, the changes of wall thickness of the left ventricular wall (LV), right ventricular wall (RV), and interventricular septal wall (IVS) were monitored from the scanning electron micrographs of each heart. The results indicated that in both STZ-C1 and STZ-C8, the diabetic hypertension could be prevented or treated by anti-hypertensive doses of cilazaprils. Besides, the values of AFR, CFR, and LVIC were significantly increased when comparing between the STZ and STZ-C1 or STZ-C8. The results of morphological examinations indicated that (1) left ventricular walls of the three hearts of STZ-rats had increased significantly more than controls. (2) Right ventricular walls and interventricular septal walls were not significantly different among STZ-rats, cilazapril treated STZ-rats and age matched controls. Therefore, it is concluded that ACE-I could act either as a cardioprotective or therapeutic agent for diabetic hearts. Both major anti-hypertension and anti-trophic effects of ACE-I have already been elucidated.