title: Endothelial nitric oxide synthase-independent effects of an ACE inhibitor on coronary flow response to bradykinin in aged mice.
abstract: 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.
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: M A Hassan
authors.initials: MA
authors.lastname: Talukder
authors.forename: Takako
authors.initials: T
authors.lastname: Fujiki
authors.forename: Keiko
authors.initials: K
authors.lastname: Morikawa
authors.forename: Minako
authors.initials: M
authors.lastname: Motoishi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Matsuo
authors.forename: Makoto
authors.initials: M
authors.lastname: Hatanaka
authors.forename: Masato
authors.initials: M
authors.lastname: Tsutsui
authors.forename: Akira
authors.initials: A
authors.lastname: Takeshita
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimokawa
mesh_terms: D000375:Aging; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D004334:Drug Administration Schedule; D004357:Drug Synergism; D007022:Hypotension / Q000139:chemically induced; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D007703:Peptidyl-Dipeptidase A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010477:Perfusion; D013841:Thiazepines / Q000494:pharmacology; D015854:Up-Regulation; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D013841:Thiazepines; C069156:temocaprilat; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496321:Nos1 protein, mouse; C496315:Nos3 protein, mouse; D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin