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IL‐10 counteracts both ET‐1 mediated vascular responses and ETA receptor expression in vivo.
Author(s) -
Giachini Fernanda Regina Casagrande,
Zemse Saiprasad,
Hilgers Rob H. P.,
Webb R. Clinton,
Tostes Rita C
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1243-c
Subject(s) - myograph , endothelin 1 , receptor , endocrinology , tumor necrosis factor alpha , in vivo , endothelin receptor , medicine , knockout mouse , stimulation , chemistry , biology , endothelium , microbiology and biotechnology
Background: We have previously reported that in vitro interleukin‐10 (IL‐10) counteracts the endothelial dysfunction induced by endothelin (ET‐1) in murine aortic rings. In this study we evaluated whether IL‐10 modulates vascular ET‐1 responses in vivo . We hypothesized that ET‐1 reactivity is exacerbated in mice lacking IL‐10 expression. Methods: Considering that vascular ET‐1 release and prepro‐ET‐1 mRNA expression are enhanced upon stimulation with tumor necrosis factor alpha (TNF‐α), C57BL6 and IL‐10 deficient male mice were treated with human recombinat TNF‐α (220 ng/Kg/day) or vehicle (saline) for 14 days. Subsequently, aortic rings were mounted in a myograph and contractile responses to endothelin‐1 (ET‐1, 10 −10 to 10 −7 M) were evaluated. Vascular ET A and ET B receptors gene expression was evaluated by RTPCR. Results: Responses to ET‐1 were almost completed abrogated in vessels from wild‐type mice infused with TNF‐α or vehicle, as well as in IL‐10 knock out mice infused with vehicle (% KCl‐induced contraction, 1.3±0.9, 0.85±0.8, 0.74±0.42, respectively; n=4). However, contractile responses to ET‐1 were enhanced (21.5±2.0%, n=4, p<0.05; Figure inserted) in IL‐10 deficient mice infused with TNF‐α. Vascular ET A receptor gene expression was significantly increased in vessels from IL‐10 knockout mice (vehicle‐ and TNF‐α‐infused mice). No significant vascular ET B receptors mRNA expression were detected in neither of the groups. Conclusions: IL‐10 counteracts both ET‐1 mediated vascular responses and ET A receptor expression in vivo . Financial Support: NIH HL‐74167, RCW; FAPESP 06/01773‐0, RCT.