title: Impaired vascular responses to relaxin in diet-induced overweight female rats.
abstract: Relaxin mediates renal and mesenteric vascular adaptations to pregnancy by increasing endothelium-dependent vasodilation and compliance and decreasing myogenic reactivity. Diet-induced overweight and obesity are associated with impaired endothelial dysfunction and vascular remodeling leading to a reduction in arterial diameter. In this study, we tested the hypothesis that local vascular responses to relaxin are impaired in diet-induced overweight female rats on a high-fat cafeteria-style diet for 9 wk. Rats were chronically infused with either relaxin or placebo for 5 days, and vascular responses were measured in isolated mesenteric arteries and the perfused kidney. Diet-induced overweight significantly increased sensitivity to phenylephrine (by 17%) and vessel wall thickness, and reduced renal perfusion flow (RPFF; by 16%), but did not affect flow-mediated vasodilation, myogenic reactivity, and vascular compliance. In the normal weight rats, relaxin treatment significantly enhanced flow-mediated vasodilation (2.67-fold), decreased myogenic reactivity, and reduced sensitivity to phenylephrine (by 28%), but had no effect on compliance or RPFF. NO blockade by l-NAME diminished most relaxin-mediated effects. In diet-induced overweight rats, the vasodilator effects of relaxin were markedly reduced for flow-mediated vasodilation, sensitivity to phenylephrine, and myogenic response compared with the normal diet rats, mostly persistent under l-NAME. Our data demonstrate that some of the vasodilator responses to in vivo relaxin administration are impaired in isolated mesenteric arteries and the perfused kidney in diet-induced overweight female rats. This does not result from a decrease in Rxfp1 (relaxin family peptide receptor) expression but is likely to result from downstream disruption to endothelial-dependent mechanisms in diet-induced overweight animals.
authors.affiliation: Dept. of Obstetrics and Gynecology, 791, Radboud Univ. Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands. j.vandrongelen@obgyn.umcn.nl
authors.forename: Joris
authors.initials: J
authors.lastname: van Drongelen
authors.forename: Arianne
authors.initials: A
authors.lastname: van Koppen
authors.forename: Jeanne
authors.initials: J
authors.lastname: Pertijs
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Gooi
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Parry
authors.forename: Fred C G J
authors.initials: FC
authors.lastname: Sweep
authors.forename: Frederik K
authors.initials: FK
authors.lastname: Lotgering
authors.forename: Paul
authors.initials: P
authors.lastname: Smits
authors.forename: Marc E A
authors.initials: ME
authors.lastname: Spaanderman
mesh_terms: D000818:Animals; D004032:Diet; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D050177:Overweight / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D018000:Receptors, Peptide / Q000378:metabolism; D012065:Relaxin / Q000378:metabolism / Q000494:pharmacology*; D012077:Renal Artery / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: C417543:RXFP1 protein, human; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D014665:Vasodilator Agents; D010656:Phenylephrine; D009569:Nitric Oxide; D012065:Relaxin; D019331:NG-Nitroarginine Methyl Ester