TY - JOUR
T1 - Impaired vascular responses to relaxin in diet-induced overweight female rats
AU - van Drongelen, Joris
AU - van Koppen, Arianne
AU - Pertijs, Jeanne
AU - Gooi, Jonathan H.
AU - Parry, Laura J.
AU - Sweep, Fred C. G. J.
AU - Lotgering, Frederik K.
AU - Smits, Paul
AU - Spaanderman, Marc E. A.
PY - 2012/3
Y1 - 2012/3
N2 - van Drongelen J, van Koppen A, Pertijs J, Gooi JH, Parry LJ, Sweep FC, Lotgering FK, Smits P, Spaanderman ME. Impaired vascular responses to relaxin in diet-induced overweight female rats. J Appl Physiol 112: 962-969, 2012. First published December 15, 2011; doi: 10.1152/japplphysiol.00470.2011.-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.
AB - van Drongelen J, van Koppen A, Pertijs J, Gooi JH, Parry LJ, Sweep FC, Lotgering FK, Smits P, Spaanderman ME. Impaired vascular responses to relaxin in diet-induced overweight female rats. J Appl Physiol 112: 962-969, 2012. First published December 15, 2011; doi: 10.1152/japplphysiol.00470.2011.-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.
KW - relaxin
KW - mesenteric arteries
KW - vasodilation
KW - myogenic reactivity
KW - arterial compliance
U2 - 10.1152/japplphysiol.00470.2011
DO - 10.1152/japplphysiol.00470.2011
M3 - Article
C2 - 22174401
SN - 8750-7587
VL - 112
SP - 962
EP - 969
JO - Journal of Applied Physiology
JF - Journal of Applied Physiology
IS - 6
ER -