Objectives Renin-angiontensin-aldosterone system (RAAS) is widely evidenced its point on inhibiting ventricular remodelling post myocardial infarction. The increasing expression of angiotensin and angiotensin-converting enzyme (ACE) post infarction and the effectiveness of angiotensin-converting enzyme inhibitor (ACEI) on inhibiting the progress of negative ventricular remodelling have been evidenced. In theory, according to the pharmacokinetic characteristics of ACEI, benazepril (Ben) with solid carboxyl has the better function, compared with captopril (Cap) with mercapto containing binding sites, because of the longer combine duration. However, its clinical eligible benefits remain to be further confirmed. In the present study, two kinds of ACEI with different binding sites were directly applied into the infarcted rat’s myocardium to explore the theoretical ACEI histocompatibility can truly achieve virtual benefit.
Methods One kind of Poly N-isopropylacrylamide thermosensitive hydrogel (PNIPAAm Gel) was synthesised and it was used as a carrier. Left anterior descending of coronary artery (LAD) in Wistar rats was ligated to make myocardial infarction models. Then, all the myocardial infarction induced rats were divided into MI + Phosphate Buffer Solution (PBS) group, MI + Gel group, MI + Gel + Cap gorup and MI + Gel + Ben group randomly. During the first five minutes after infarction, 100 μl PBS (1mmol/L, pH 7.4), 100 μl 3% (w/w) Gel solution, 100 μl 3% (w/w) Gel with Cap (50 mg/ml) solution and 100 μl 3% (w/w) Gel with Ben (10 mg/ml) solution was injected into the infarcted myocardium as designed, respectively. Rats in sham operation group received the same process, except for the LAD were not ligated. All rats were fed for ninety days and then received ultrasonic cardiogram, haemodynamics and isolated myocardium contraction ability test. Then heart tissue was used to test the expression of angiotensin-II (Ang-II) and angiotensin-converting enzyme (ACE) by Elisa.
Results The expression of Ang-II and ACE was significantly increased post MI, but ACEI can reduce the value significantly and the performance of Ben was the best among the Gel and Gel/ACEI treated groups [Ang-II: MI + Gel + Cap (803.89 ± 89.47) ng/ml, MI + Gel + Ben (5418.46 ± 56.32) ng/ml, MI + Gel (1137.15 ± 119.33) ng/ml vs. MI + PBS (1304.17 ± 119.87) ng/ml; ACE: MI + Gel (102.68 ± 4.04) ng/ml, MI + Gel + Cap (91.03 ± 5.7) ng/ml, MI + Gel + Ben (83.31 ± 0.55) ng/ml vs. MI + PBS (115.66 ± 5.51) ng/ml, P < 0.05 for all comparison]. While, on the aspect of inhibiting left ventricular expansion, increasing the rate pressure change in the left ventricular, enhancing the contraction force of isolated myocardium, Gel/ACEI groups performed better than Gel alone group [LVEDD: MI + Gel + Cap (6.98 ± 0.01) mm, MI + Gel + Ben (7.08 ± 0.36) mm, MI + Gel (7.71 ± 0.25) mm vs. MI + PBS (10.76 ± 0.49) mm; Dp/Dt: MI + Gel + Cap (6195.81 ± 68.28) mmHg/s, MI + Gel + Ben (5418.46 ± 64.76) mmHg/s, MI + Gel (3925.05 ± 73.74) mmHg/s vs. MI + PBS (2596.94 ± 253.85) mmHg/s; Contraction Force: MI + Gel + Cap (107.14 ± 1.67) mg, MI + Gel + Ben (106.8 ± 6.98) mg, MI + Gel (80.81 ± 4.96) mg vs. MI + PBS (40.27 ± 0.85) mg; P < 0.05 for all comparison]. However, there was no significant difference between Ben/Gel treated and Cap/Gel treated rat’s hearts.
Conclusions Benazepril with higher histocompatibility can achieve the better function on inhibiting Ang-II and ACE expression post MI, but the pharmacokinetic ACEI high tissue affinity can not realise the effective improvement of infarcted heart’s structure and function.