title: Increased superoxide production and altered nitric oxide-mediated relaxation in the aorta of young but not old male relaxin-deficient mice.
abstract: The vascular effects of exogenous relaxin (Rln) treatment are well established and include decreased myogenic reactivity and enhanced relaxation responses to vasodilators in small resistance arteries. These vascular responses are reduced in older animals, suggesting that Rln is less effective in mediating arterial function with aging. The present study investigated the role of endogenous Rln in the aorta and the possibility that vascular dysfunction occurs more rapidly with aging in Rln-deficient (Rln(-/-)) mice. We compared vascular function and underlying vasodilatory pathways in the aorta of male wild-type (Rln(+/+)) and Rln(-/-) mice at 4 and 16 mo of age using wire myography. Superoxide production, but not nitrotyrosine or NADPH oxidase expression, was significantly increased in the aorta of young Rln(-/-) mice, whereas endothelial nitric oxide (NO) synthase and basal NO availability were both significantly decreased compared with Rln(+/+) mice. In the presence of the cyclooxygenase inhibitor indomethacin, sensitivity to ACh was significantly decreased in young Rln(-/-) mice, demonstrating altered NO-mediated relaxation that was normalized in the presence of a membrane-permeable SOD or ROS scavenger. These vascular phenotypes were not exacerbated in old Rln(-/-) mice and, in most cases, did not differ significantly from old Rln(+/+) mice. Despite the vascular phenotypes in Rln(-/-) mice, endothelium-dependent and -independent vasodilation were not adversely affected. Our data show a role for endogenous Rln in reducing superoxide production and maintaining NO availability in the aorta but also demonstrate that Rln deficiency does not compromise vascular function in this artery or exacerbate endothelial dysfunction associated with aging.
authors.affiliation: School of BioSciences, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Hooi H
authors.initials: HH
authors.lastname: Ng
authors.affiliation: School of BioSciences, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Maria
authors.initials: M
authors.lastname: Jelinic
authors.affiliation: School of BioSciences, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Parry
authors.affiliation: School of BioSciences, The University of Melbourne, Parkville, Victoria, Australia chen.leo@unimelb.edu.au.
authors.forename: Chen-Huei
authors.initials: CH
authors.lastname: Leo
mesh_terms: D000367:Age Factors; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005838:Genotype; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010641:Phenotype; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012065:Relaxin / Q000172:deficiency* / Q000235:genetics; D012737:Sex Factors; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; C478103:RXFP1 protein, mouse; D043562:Receptors, G-Protein-Coupled; D014665:Vasodilator Agents; D013481:Superoxides; D009569:Nitric Oxide; D012065:Relaxin; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse
keywords: aorta; endothelium; nitric oxide; relaxin; superoxide