Endothelial nitric oxide synthase-independent effects of an ACE inhibitor on coronary flow response to bradykinin in aged mice

ACE inhibitors are known to ameliorate cardiovascular complications in aging; however, their effects on the coronary circulation in relation to aging and eNOS dependence remain to be examined. Coronary flow responses to bradykinin with or without ACE inhibitors were examined in Langendorff-perfused hearts from young (16-20 weeks) and aged (16-20 months) control and eNOS^-/- mice. Western blot analysis was performed for cardiac eNOS, nNOS, and ACE. Baseline coronary flow was comparable between young and aged mice of both strains. Aging did not affect bradykinin-induced coronary flow in either strain. Interestingly, both acute and chronic treatment with an ACE inhibitor markedly augmented the flow response in aged control and eNOS^-/- mice. Aged eNOS^-/- mice were markedly hypertensive and had larger ventricular mass than control mice. The antihypertensive effect of temocapril was greater in aged eNOS^-/- mice, associated with reduction in the ventricular weight in both strains. Western blot analysis demonstrated an increased expression of eNOS in aged control mice, and ACE expression was increased in eNOS^-/- mice. These results indicate that coronary flow response to bradykinin is preserved in aged mice even in the absence of eNOS, and an ACE inhibitor augments this response by both eNOS-dependent and -independent mechanisms.