title: Aging attenuates the vasodilator response to relaxin.
abstract: Relaxin, an insulin-like growth factor peptide, increases endothelium-dependent vasodilation and vascular compliance and decreases myogenic reactivity. These vascular effects significantly contribute to the physiological circulatory adaptations in pregnancy, particularly in the mesentery and kidney. Aging predisposes to vascular maladaptation and gestational hypertensive disease. We hypothesized that mild aging reduces the vascular responses to relaxin. In 20 young (10-12 wk) and 20 middle-aged (40-46 wk) female Wistar Hannover rats, vascular responses to chronic exposure of relaxin vs. placebo (5 days) were quantified in isolated mesenteric arteries and kidney. Vascular responses were evaluated using pressure-perfusion myograph, wire myograph, and an isolated perfused rat kidney model. Rxfp1 (relaxin family peptide) gene expression was determined by quantitative polymerase chain reaction. In young rats, relaxin stimulated nitric oxide (NO)-dependent flow-mediated vasodilation (2.67-fold, from 48 ± 9 to 18 ± 4 μl/min), reduced myogenic reactivity (from -1 ± 2 to 7 ± 3 μm/10 mmHg), and decreased mesenteric sensitivity to (28%, from 1.39 ± 0.08 to 1.78 ± 0.10 μM) but did not change compliance and renal perfusion flow (RPFF). In aged rats, relaxin did not affect any of the analyzed mesenteric or renal parameters. In aged compared with young placebo-treated rats, all mesenteric characteristics were comparable, while RPFF was lower (17%, from 6.9 ± 0.2 to 5.7 ± 0.1 ml·min⁻¹·100 g⁻¹) even though NO availability was comparable. Rxfp1 expression was not different among young and aged rats. Our findings suggest that moderate aging involves normal endothelial function but blunts the physiological endothelium-dependent and -independent vasodilator response to relaxin.
authors.affiliation: Dept. of Obstetrics and Gynecology, Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands. j.vandrongelen@obgyn.umcn.nl
authors.forename: Joris
authors.initials: J
authors.lastname: van Drongelen
authors.forename: Ivo H J
authors.initials: IH
authors.lastname: Ploemen
authors.forename: Jeanne
authors.initials: J
authors.lastname: Pertijs
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Gooi
authors.forename: Fred C G J
authors.initials: FC
authors.lastname: Sweep
authors.forename: Frederik K
authors.initials: FK
authors.lastname: Lotgering
authors.forename: Marc E A
authors.initials: ME
authors.lastname: Spaanderman
authors.forename: Paul
authors.initials: P
authors.lastname: Smits
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D023421:Models, Animal; D009569:Nitric Oxide / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012065:Relaxin / Q000494:pharmacology*; D012077:Renal Artery / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology*
chemical_list: D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D009569:Nitric Oxide; D012065:Relaxin