Losartan reduces collagen content and intimal thickening of iliac arteries after balloon injury in rabbits

Intimal thickening and formation of extracellular matrix are parts of the repair process after vascular injury. Similar processes occur after coronary angioplasty. Prior studies have shown that losartan inhibits intimal thickening in rat carotid arteries following balloon injury. However, the effects of losartan in reducing the collagen content of arteries after balloon injury have not been examined. The objectives of this study were to determine the change in collagen content after balloon injury and to analyse the mechanisms of reduction of collagen content and intimal thickening. Losartan (15 mg/kg/d) was administered orally from six days before to eight weeks after balloon injury in rabbits. Collagen content was measured histologically by the use of circularly polarised images of picrosirius red-stained sections. Collagen content in arterial intima was found to be significantly lower in the losartan-treated group (n=12) than in the control group (n=12) (21.6%±5.2% vs. 43.8%±7.6%, p<0.01). Losartan reduced the collagen content in arterial intima by 50.7% area fraction compared with that of control. The morphological observation showed that the intimal area and intimal-to-medial area ratio in the losartan-treated group were significantly less than in the control group (0.27±0.13mm 2 vs. 0.52±0.29 mm 2 , 0.55±0.21 vs. 0.97±0.25, respectively, p<0.05). These data indicate that losartan reduces vascular collagen content and inhibits intimal thickening after balloon injury. The results also suggest that collagen accumulation in the intima may be an important factor in the development of the stenotic lesion and that the use of losartan may have therapeutic value to prevent stenosis after balloon injury.