Mechanism For The Prevention Of Myocardial Fibrosis In Hypertensive Rats With Abdominal Aortic Constriction By Telmisartan And Amlodipine Besylate

Objective:To evaluate the preventive effects of Telmisartan and Amlodipine on myocardial f ibrosis in hypertensive rats with abdominal aortic constriction (AAC), and to find out their serum levels of angiotensin-(1-7) [Ang-(1?7)].Methods:AAC and sham operation were performed on 8-week-old male Sprague Dawley rats. After one week of operation, AAC rats were randomly divided into three groups, Telmisartan, Amlodipine and AAC control respectively. The first two groups were treated by Telmisartan and Amlodipine at the dosages of 5mg-kg-1·d-1 respectively. After 8 week, serum levels of Ang-(l-7) were determined by ELISA. Myocardial collagen volume fraction (CVF), collagen type I, type III and?/?were assessed by Sirius red staining combined with computer image analysis.Results:Compared with sham group, myocardial CVF, integral optical density(IOD) values of collagen type?and?/?in turn increased in Telmisartan group, Amlodipine group and AAC control group (p<0.05). Treatment groups were significantly lower than AAC control group, and Telmisartan group was significantly lower than Amdlodipine group. IOD values of collagen type III also were on the rise, and Treatment groups were significantly lower than AAC control group, however, there were no significant difference between Telmisartan group and Amlodipine group. Compared with AAC control group, Telmisartan significantly increased serum levels of Ang-(1-7) (p<0.05), and Amlodipine also increased serum levels ot Ang-(1-7), nowever inere (?) (?) (?) (?) between tnem. Relationships between serum levels of Ang-(1-7) and myocardial CVF, TOD values of collagen type?and type?,?/?were negatively correlated (p<0O.05).Conclusion:Teimisartan and amiodipine could be used to prevent myocardial fibrosis in hypertensive rats with AAC, and it seems that Telmisartan is better than Amiodipine in preveting myocardial fibrosis, and Ang-(1-7) may be involved in the process of inhibiting myocardial fibrosis with Telmisartan. Objective:To observe the changes of gelatinases(MMP-2, MMP-9) and nuclear factor-kappa B (NF-?B)during myocardial fibrosis and therapy with Telmisartan and Amlodipine in hypertensive rats with abdominal aortic constriction(AAC), and to explore the mechanism of pharmaceutical prevention of myocardial fibrosis.Methods:AAC and sham operation were performed on 8-week-old male Sprague Dawley rats. After one week of operation, AAC rats were randomly divided into three groups, Telmisartan, Amlodipine and AAC control respectively. The first two groups were treated by Telmisartan and Amlodipine at the dosages of 5mg·kg-1·d-1'respectively. After 8 weeks, Myocardial collagen volume fraction(CVF), collagen type?, type III and?/?were assessed by sirius red staining combined with computer image analysis; Activity of MMP-2 and MMP-9 was performed by gelatin zymography; Protein levels of MMP-2, MMP-9 and NF-?B were assessed by Western-blot.Results:Compared with sham group, myocardial CVF, integral optical density (IOD) values of collagen type I and?/?increased in Telmisartan group, Amlodipine group and AAC control group (p<0.05). Treatment groups were significantly lower than AAC control group (p<0.05), and Telmisartan group was significantly lower than Amdlodipine group (p<0.05). IOD values of collagen type III also were on the rise, and Treatment groups were significantly lower than AAC control group (p<0.05), however, there were no significant difference between Telmisartan group and Amlodipine group. Activity of MMP-2 between Telmisartan group and Amlodipine group were no significant difference, which was lower than that in AAC control group and higher than that in sham group (P<0.05). Compared with sham group, activity of MMP-9 and protein levels of MMP-2 and MMP-9 increased in Telmisartan group, Amlodipine group and AAC control group (P<0.05). Protein levels of NF-?B in Telmisartan group were lower than those in Amlodipine group, and protein levels of NF-?B in Amlodipine group were higher than those in sham group, and there were no significant difference between Telmisartan group and sham group.Conclusion:Both telmisartan and amlodipine can prevent myocardial fibrosis in hypertensive rats with AAC by inhibiting gelatinases, and its effects seem to be more effective for telmisartan. NF-?B may be involved in the process of inhibiting gelatinases with telmisartan.