Prevention of Amlodipine with ALT-711 on target organs remodeling in Spontaneously Hypertensive Rats / 中国综合临床

ABSTRACT

Objective To investigate the intervention of Amlodipine combined with alanine aminotransferase(ALT)-711 on blood pressure and preventing of target organ remodels of Spontaneously Hypertensive Rats(SHR),and to explore an optimized treatment design.Methods A total of 24 SHRs at 12-Week-old male were randomly divided into 4 groups,with 6 SHRs in each group.In the control group(Group A)the SHR were given normal saline 1 ml/(kg · d)via intragastric administration; the SHRs in Group B were treated with Amlodipine 1 mg/(kg · d) via ntragastric administration; the SHRs in Group C were treated with ALT-711 10 mg/(kg · d)via ntragastric administration;the SHRs were treated with Amlodipine 1 mg/(kg · d)combined with ALT-711 10 mg/(kg · d)via ntragastric administration in Group D.All groups were treated for 8 weeks,and the blood pressure in mouse tail were monitored.After 8 weeks,all SHRs were executed in the condition of anaesthedia.Right cervical artery,heart and kidney were measured through immunohistochemistry,histological stain and imagine analysis.The remodeling of vascular,heart,kidney were compared,and collagen volume fraction,advanced glycation end products (AGEs) and fibronectin (FN) expression were measured.Results (1) After treatment for 8 weeks,blood pressure of SHRs in the 4 groups were (184.72 + 15.14),(108.00 ±10.19),(155.64±10.03)and (99.83 ± 12.27) nun Hg in Group A,B,C and D,respectively.The blood pressure in Group D was the lowest in the 4 groups (F =14.6702,P ＜ 0.05),whereas it is not significantly different from Group B (P ＞ 0.05).(2) The mean thickness of carotid arteries were (0.450 ± 0.023),(0.380 ±0.021),(0.420 ±0.019) and (0.320 ±0.020) mm in Group A,B,C and D,respectively.The mean thickness of carotid arteries in Group D was the lowest in the 4 groups(F =4.1463,P ＜0.05).(3).The mean intimal area of carotid arteries were (19.0 + 1.3) × 105,(25.0 ± 1.4) × 105,(29.8 + 1.5) × 105 and (21.3 ±1.3) × l05 μm2 in Group A,B,C and D,respectively.The mean intimal area of carotid arteries in Group D was significantly smallest than the other 3 groups(F =4.4305,P ＜0.05).(4) The collagen content in different organs in the 4 groups after treatment 8 weeks:in carotid arteries,they were (6.25 ± 0.19)％,(3.56 ± 0.03) ％,(4.25 ± 0.12) ％ and (1.32 ± 0.05) ％ in Group A,B,C and D,respectively.The collagen content in Group D were significantly lower than the other 3 groups (F =4.9316,P ＜ 0.01).In myocardia:collagen content in Group A,B,C and D were (6.02 ± 0.21)％,(4.08 ± 0.14)％,(4.44 ± 0.11)％ and (1.13 ± 0.08) ％ respectively,and it was the lowest in Group D (F =4.2469,P ＜ 0.01).In kidney,the collagen content in Group A,B,C and D were (13.23 ±0.51)％,(7.28 ±0.35)％,(8.33 ±0.22)％ and (5.66 ±0.13)％ respectively,and it was the lowest in Group D(F=8.1038,P ＜0.01).(5).Express rate of AGEs in carotid arteries in Group A,B,C and D were (31.48 ±7.30)％,(20.55 ±5.91)％,(10.48 ±0.98)％ and (7.56 ± 0.68) ％ respectively,with the lowest expression in Group D (F =11.4537,P ＜ 0.01).Express rate of FN in carotid arteries in Group A,B,C and D group were (28.18 ±5.66)％,(17.26 ±5.83)％,(18.20 ±1.44) ％ and (15.12 ± 1.03) ％ respectively,with the lowest expression in Group D (F =9.0036,P ＜ 0.01).Conclusion Amlodipine combined with ALT-711 decreased blood pressure more effectively and prevented the remodel of target organ in SHRs than Amlodipine or ALT-711 alone.