title: Localization of relaxin receptors in arteries and veins, and region-specific increases in compliance and bradykinin-mediated relaxation after in vivo serelaxin treatment.
abstract: Relaxin is a potent vasodilator of small resistance arteries and modifies arterial compliance in some systemic vascular beds, yet receptors for relaxin, such as RXFP1, have only been localized to vascular smooth muscle. This study first aimed to localize RXFP1 in rat arteries and veins from different organ beds and determine whether receptors are present in endothelial cells. We then tested the hypothesis that region-specific vascular effects of relaxin may be influenced by the cellular localization of RXFP1 within different blood vessels. The aorta, vena cava, mesenteric artery, and vein had significantly higher (P<0.05) RXFP1 immunostaining in endothelial cells compared with vascular smooth muscle, whereas the femoral artery and vein and small pulmonary arteries had higher (P<0.01) RXFP1 immunostaining in the vascular smooth muscle. Male rats were treated subcutaneously with recombinant human relaxin-2 (serelaxin; 4 μg/h) for 5 d; vasodilation and compliance in mesenteric and femoral arteries and veins were compared with placebo controls. Serelaxin significantly (P=0.04) reduced wall stiffness and increased volume compliance in mesenteric arteries but not in the other vessels examined. This was associated with changes in geometrical properties, and not compositional changes in the extracellular matrix. Serelaxin treatment had no effect on acetylcholine-mediated relaxation but significantly (P<0.001) enhanced bradykinin (BK)-mediated relaxation in mesenteric arteries, involving enhanced nitric oxide but not endothelium-derived hyperpolarization or vasodilatory prostanoids. In conclusion, there is differential distribution of RXFP1 on endothelial and smooth muscle across the vasculature. In rats, mesenteric arteries exhibit the greatest functional response to chronic serelaxin treatment.
authors.affiliation: 2Department of Zoology, The University of Melbourne, Parkville, VIC, 3010, Australia. ljparry@unimelb.edu.au.
authors.forename: Maria
authors.initials: M
authors.lastname: Jelinic
authors.forename: Chen-Huei
authors.initials: CH
authors.lastname: Leo
authors.forename: Emiel D
authors.initials: ED
authors.lastname: Post Uiterweer
authors.forename: Shaun L
authors.initials: SL
authors.lastname: Sandow
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Gooi
authors.forename: Mary E
authors.initials: ME
authors.lastname: Wlodek
authors.forename: Kirk P
authors.initials: KP
authors.lastname: Conrad
authors.forename: Helena
authors.initials: H
authors.lastname: Parkington
authors.forename: Marianne
authors.initials: M
authors.lastname: Tare
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Parry
mesh_terms: D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000378:metabolism*; D001920:Bradykinin / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D018000:Receptors, Peptide / Q000378:metabolism*; D012065:Relaxin / Q000494:pharmacology*; D014680:Veins / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; C033395:relaxin receptors; D012065:Relaxin; D001920:Bradykinin
keywords: RXFP1; vasodilation
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