title: Ghrelin-related peptides do not modulate vasodilator nitric oxide production or superoxide levels in mouse systemic arteries.
abstract: The ghrelin gene is expressed in the stomach where it ultimately encodes up to three peptides, namely, acylated ghrelin, des-acylated ghrelin and obestatin, which all have neuroendocrine roles. Recently, the authors' reported that these peptides have important physiological roles in positively regulating vasodilator nitric oxide (NO) production in the cerebral circulation, and may normally suppress superoxide production by the pro-oxidant enzyme, Nox2-NADPH oxidase. To date, the majority of studies using exogenous peptides infer that they may have similar roles in the systemic circulation. Therefore, this study examined whether exogenous and endogenous ghrelin-related peptides modulate NO production and superoxide levels in mouse mesenteric arteries and/or thoracic aorta. Using wire myography, it was found that application of exogenous acylated ghrelin, des-acylated ghrelin or obestatin to mouse thoracic aorta or mesenteric arteries failed to elicit a vasorelaxation response, whereas all three peptides elicited vasorelaxation responses of rat thoracic aorta. Also, none of the peptides modulated mouse aortic superoxide levels as measured by L-012-enhanced chemiluminescence. Next, it was found that NO bioactivity and superoxide levels were unaffected in the thoracic aorta from ghrelin-deficient mice when compared with wild-type mice. Lastly, using novel GHSR-eGFP reporter mice in combination with double-labelled immunofluorescence, no evidence was found for the growth hormone secretagogue receptor (GHSR1a) in the throracic aorta, which is the only functional ghrelin receptor identified to date. Collectively these findings demonstrate that, in contrast to systemic vessels of other species (e.g. rat and human) and mouse cerebral vessels, ghrelin-related peptides do not modulate vasodilator NO production or superoxide levels in mouse systemic arteries.
authors.affiliation: Vascular Biology & Immunopharmacology Group, Department of Pharmacology, Monash University, Melbourne, Victoria, Australia.|School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria, Australia.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Ku
authors.affiliation: Department of Physiology, Monash University, Melbourne, Victoria, Australia.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Sleeman
authors.affiliation: Department of Physiology, Monash University, Melbourne, Victoria, Australia.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Sobey
authors.affiliation: Department of Physiology, Monash University, Melbourne, Victoria, Australia.
authors.forename: Zane B
authors.initials: ZB
authors.lastname: Andrews
authors.affiliation: School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria, Australia.
authors.forename: Alyson A
authors.initials: AA
authors.lastname: Miller
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D054439:Ghrelin / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D054440:Receptors, Ghrelin / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D054439:Ghrelin; D054440:Receptors, Ghrelin; C422650:ghrelin, des-n-octanoyl; D013481:Superoxides; D009569:Nitric Oxide
keywords: GHSR1a; ghrelin; nitric oxide; superoxide; systemic arteries