Abstract

The objective of this study was to investigate the effect of amlodipine combined with ALT-711 on hypertension and the prevention of the complication of hypertension such as arteriosclerosis. Ten-week-old male spontaneously hypertensive rats (SHR) were randomly divided into four groups with six in each group: the blank control group (Group A, physiological saline 1 ml/kg/d), the amlodipine group (Group B, amlodipine 1 mg/kg/d), the ALT-711 group (Group C, ALT-711 10 mg/kg/d ), and the ALT-711 + amlodpine group (Group D amlodipine 1 mg/kg/d and ALT-711 10 mg/kg/d). Eight week later, the aorta was harvested and sliced with stain of Masson solution, Collagen volume fraction was measured by image analysis. The expressions of advanced glycation end-products (AGEs), integrin β1, fibronectin (FN) on the slice in each group were measured by immunohistochemistry and western blot were assessed. The artery mechanical strength in all groups was compared and the carotid artery rupture pressure was measured. Compared to Group A, the blood pressure of Group B, C and D significantly decreased. The positive expressions of AGEs, intergrin β1 and FN in Group D significantly decreased compared to Group A, B or C (P<0.0134), and the pressure rupture of carotid artery, the blank control group (group A) were the lowest, and amlodipine combined with ALT-711 group (D group) is the highest among 4 groups and higher than amlodipine and ALT-711 alone (p<0.0012). However, ALT-711 combined with amlodipine can improve artery mechanical strength and prevent the aortic wall from extracellular matrix remodel in SHRs than amlodipine alone.

Key words: ALT-711, amlodipine, arteriosclerosis, age.