title: Sites of action of ghrelin receptor ligands in cardiovascular control.
abstract: Circulating ghrelin reduces blood pressure, but the mechanism for this action is unknown. This study investigated whether ghrelin has direct vasodilator effects mediated through the growth hormone secretagogue receptor 1a (GHSR1a) and whether ghrelin reduces sympathetic nerve activity. Mice expressing enhanced green fluorescent protein under control of the promoter for growth hormone secretagogue receptor (GHSR) and RT-PCR were used to locate sites of receptor expression. Effects of ghrelin and the nonpeptide GHSR1a agonist capromorelin on rat arteries and on transmission in sympathetic ganglia were measured in vitro. In addition, rat blood pressure and sympathetic nerve activity responses to ghrelin were determined in vivo. In reporter mice, expression of GHSR was revealed at sites where it has been previously demonstrated (hypothalamic neurons, renal tubules, sympathetic preganglionic neurons) but not in any artery studied, including mesenteric, cerebral, and coronary arteries. In rat, RT-PCR detected GHSR1a mRNA expression in spinal cord and kidney but not in the aorta or in mesenteric arteries. Moreover, the aorta and mesenteric arteries from rats were not dilated by ghrelin or capromorelin at concentrations >100 times their EC(50) determined in cells transfected with human or rat GHSR1a. These agonists did not affect transmission from preganglionic sympathetic neurons that express GHSR1a. Intravenous application of ghrelin lowered blood pressure and decreased splanchnic nerve activity. It is concluded that the blood pressure reduction to ghrelin occurs concomitantly with a decrease in sympathetic nerve activity and is not caused by direct actions on blood vessels or by inhibition of transmission in sympathetic ganglia.
authors.affiliation: Department of Anatomy & Neuroscience, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Brid
authors.initials: B
authors.lastname: Callaghan
authors.forename: Billie
authors.initials: B
authors.lastname: Hunne
authors.forename: Haruko
authors.initials: H
authors.lastname: Hirayama
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Sartor
authors.forename: Trung V
authors.initials: TV
authors.lastname: Nguyen
authors.forename: Fe C
authors.initials: FC
authors.lastname: Abogadie
authors.forename: Dorota
authors.initials: D
authors.lastname: Ferens
authors.forename: Peter
authors.initials: P
authors.lastname: McIntyre
authors.forename: Kung
authors.initials: K
authors.lastname: Ban
authors.forename: Jonathan
authors.initials: J
authors.lastname: Baell
authors.forename: John B
authors.initials: JB
authors.lastname: Furness
authors.forename: James A
authors.initials: JA
authors.lastname: Brock
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000294:innervation / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002319:Cardiovascular System / Q000294:innervation*; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000502:physiology*; D054439:Ghrelin / Q000378:metabolism* / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D008024:Ligands; D008297:Male; D008638:Mesenteric Arteries / Q000294:innervation / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D054440:Receptors, Ghrelin / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: C433143:CP 424391; D054439:Ghrelin; C571124:Ghsr1a protein, rat; D008024:Ligands; D010880:Piperidines; D011720:Pyrazoles; D012333:RNA, Messenger; D054440:Receptors, Ghrelin; D049452:Green Fluorescent Proteins