Impaired vascular responses to relaxin in diet-induced overweight female rats
Authorvan Drongelen, J; van Koppen, A; Pertijs, J; Gooi, JH; Parry, LJ; Sweep, FCGJ; Lotgering, FK; Smits, P; Spaanderman, MEA
Source TitleJournal of Applied Physiology
PublisherAMER PHYSIOLOGICAL SOC
Document TypeJournal Article
Citationsvan Drongelen, J., van Koppen, A., Pertijs, J., Gooi, J. H., Parry, L. J., Sweep, F. C. G. J., Lotgering, F. K., Smits, P. & Spaanderman, M. E. A. (2012). Impaired vascular responses to relaxin in diet-induced overweight female rats. JOURNAL OF APPLIED PHYSIOLOGY, 112 (6), pp.962-969. https://doi.org/10.1152/japplphysiol.00470.2011.
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C1 - Journal Articles Refereed
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.
KeywordsReproduction; Systems Physiology; Expanding Knowledge in the Medical and Health Sciences; Reproductive System and Disorders
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