Effects of age on angiotensin II response and antagonistic activity of losartan in rat aorta and liver

Abstract

The present study was undertaken to investigate the effects of age on angiotensin II (All) response and antagonistic activity of losartan using aortic rings and liver homogenates from rats ranging in age from 0.7 to 20 months. Whether the endothelium was present or not, the maximum contractile response to All decreased with age. Removal of the endothelium enhanced All-induced maximum contraction and these endothelial effects seemed to be due to endothelium-derived relaxing factor (EDRF) in all ages. Equilibrium binding studies demonstrated an age-related decrease in maximum binding (Bmax) with little change in binding affinity (Kd). In rat aorta, the extent of losartan-induced parallel shifts (KB) in All concentration-response curves was not significantly different between ages. In addition, IC50 value of losartan in competition binding was not changed with age in rat liver homogenates. These results suggest that the potency of losartan is not altered with age in rat aorta and liver, although All-induced contractile response and the maximum All binding decreased significantly with age.