title: Early aging and anatomic heterogeneity determine cyclooxygenase-mediated vasoconstriction to angiotensin II in mice.
abstract: We previously reported that angiotensin II (AngII)-induced vasoconstriction involves activation of cyclooxygenase (COX) in murine aorta and carotid artery. The aim of this study was to investigate the roles of early aging and COX in AngII-induced vasoconstriction in different vascular beds. Aortic, carotid, renal, and femoral artery rings of 19- and 34-week-old C57BL/6 mice were pretreated with the nitric oxide synthase inhibitor L-NAME (300 micromol/L) to exclude effects of NO. Contractions to AngII (100 nmol/L) were recorded in the presence or absence of meclofenamate (10 micromol/L), a nonselective COX inhibitor. The results indicate a pronounced heterogeneity in the vascular responsiveness to AngII. Renal and femoral artery rings showed stronger contractions than aorta or carotid artery (P < 0.01 for both). In all vessels of young animals COX inhibition with meclofenamate only partially blocked vasoconstriction to AngII, whereas contractions were completely abolished in the aorta and carotid artery of older mice (P < 0.05 vs untreated for both). These data demonstrate that COX determines AngII-induced vasoconstriction in the mouse aorta and carotid artery during the early physiological aging process, independent of endothelial NO bioactivity. AngII-induced vasoconstriction in vessels more distal to the heart such as femoral and renal arteries is only in part mediated by COX-dependent mechanisms that remain unaffected by early aging.
authors.affiliation: Department of Medicine, Internal Medicine I, Medical Policlinic, University Hospital, Zürich, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Kretz
authors.forename: Alexa L
authors.initials: AL
authors.lastname: Mundy
authors.forename: Corinne C
authors.initials: CC
authors.lastname: Widmer
authors.forename: Matthias
authors.initials: M
authors.lastname: Barton
mesh_terms: D000375:Aging / Q000502:physiology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001808:Blood Vessels / Q000033:anatomy & histology*; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D000804:Angiotensin II; D009569:Nitric Oxide; D008469:Meclofenamic Acid; D011451:Prostaglandin-Endoperoxide Synthases