imidapril and Atherosclerosis

Recent evidence indicates that renin-angiotensin system (RAS) plays an important role in the pathogenesis of atherosclerosis. It was reported that inhibition of RAS with angiotensin II type 1 receptor blockers (ARBs) or angiotensin converting enzyme inhibitors (ACEIs) is effective in prevention of atherosclerosis. Here, we investigated the effects of an ARB or/and an ACEI on atherosclerosis development and periadventitial inflammation in apolipoprotein E (ApoE)-deficient mice. RT-PCR revealed that major RAS components were expressed in periaortic tissue. Ang II infusion significantly increased accumulation of bone marrow derived cells into both neointima (p<0.05) and periaortic tissue (p<0.01). Male ApoE- deficient mice were treated with either vehicle, TA606A (10mg/kg/day, ARB), imidapril (3mg/kg/day, ACEI) or TA606A plus imidapril (TA606A 10mg/kg/day+imidapril 3mg/kg/day, ARB+ACEI) for 24 weeks starting at 12 weeks of age. ARB, ACEI, and ARB+ACEI significantly reduced atherosclerotic lesion formation in aorta compared with vehicle (p<0.05), with reduced expression of monocyte chemoattractant protein-1 in periaortic tissues (p<0.01). Neither blood pressure nor heart rate was changed by the treatments at these lower doses. Imidapril significantly reduced lipid deposition in atheroma and plasminogen activator inhibitor-1 expression in periadventitial tissue (p<0.05, respectively). Imidapril and combination therapy significantly attenuated macrophage infiltration into the atherosclerotic plaque (p<0.05, respectively). All treatments reduced macrophage accumulation in the periadventitial tissue 12 weeks after treatment (p<0.05, respectively). These results suggest that inhibition of renin-angiotensin system attenuates periadventitial inflammation and reduces atherosclerotic lesion formation.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Aorta; Apolipoproteins E; Atherosclerosis; Chemokine CCL2; Connective Tissue; Gene Expression Regulation; Imidazoles; Imidazolidines; Inflammation; Male; Mice; Mice, Knockout; Pyridines; Renin-Angiotensin System; Tetrazoles

Angiotensin receptor blockers (ARB) have been emerging as drugs to treat atherosclerosis. The effectiveness of the ARB losartan at reducing atherosclerosis was compared with that of ACE inhibitors in hypertensive patients. A total of 50 patients with hypertension were divided into 3 groups: a control group receiving neither an ARB nor an ACE inhibitor (n = 14), a losartan group (n = 22) receiving 50 mg/day of losartan, and an ACE inhibitor group (n = 14) receiving either 5 mg/day of enalapril or 5 mg/day of imidapril. Atherosclerosis was evaluated based on the intima-media thickness (IMT) of the common carotid artery measured by B-mode ultrasound at baseline and after approximately 12 months of treatment. After the treatment, IMT significantly decreased with losartan (from 0.87 +/- 0.14 to 0.79 +/- 0.16 mm, P < 0.05) and with ACE inhibitor (from 0.81 +/- 0.14 to 0.74 +/- 0.11 mm, P < 0.05). The reduction was comparable between the two groups, -0.078 +/- 0.136 with losartan and -0.073 +/- 0.109 mm with ACE inhibitor, and the rate of the reduction was similar between the two drugs; -0.098 +/- 0.142 mm/year with losartan and (-0.076 +/- 0.118 mm/year) with ACE inhibitor. On the contrary, IMT did not change in the control group (from 0.90 +/- 0.20 to 0.95 +/- 0.26 mm) during the treatment period. Concomitant medication and coronary risk factors such as hyperlipidemia, diabetes mellitus, and smoking did not differ significantly among the groups. The antiatherosclerotic effect of losartan on the carotid artery was comparable to that of ACE-inhibitors, and less adverse effects, such as coughing that occurs with ACE inhibitors, were observed. Losartan appears to be a better alternative to ACE inhibitors for treating atherosclerosis in Japanese hypertensive patients.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Atherosclerosis; Carotid Artery, Common; Enalapril; Humans; Hypertension; Imidazolidines; Losartan; Middle Aged; Tunica Intima; Tunica Media; Ultrasonography