TY - JOUR
T1 - Endothelial nitric oxide synthase-independent effects of an ACE inhibitor on coronary flow response to bradykinin in aged mice
AU - Talukder, M. A.Hassan
AU - Fujiki, Takako
AU - Morikawa, Keiko
AU - Motoishi, Minako
AU - Matsuo, Yoko
AU - Hatanaka, Makoto
AU - Tsutsui, Masato
AU - Takeshita, Akira
AU - Shimokawa, Hiroaki
PY - 2004/11
Y1 - 2004/11
N2 - 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.
AB - 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.
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U2 - 10.1097/00005344-200411000-00007
DO - 10.1097/00005344-200411000-00007
M3 - Article
C2 - 15505492
AN - SCOPUS:7444227939
SN - 0160-2446
VL - 44
SP - 557
EP - 563
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
IS - 5
ER -