TY - JOUR
T1 - Estradiol receptors agonists induced effects in rat intestinal microcirculation during sepsis
AU - Sharawy, Nivin
AU - Ribback, Silvia
AU - Al-Banna, Nadia
AU - Lehmann, Christian
AU - Kern, Hartmut
AU - Wendt, Michael
AU - Cerny, Vladimir
AU - Dombrowski, Frank
AU - Pavlovic, Dragan
PY - 2013/1
Y1 - 2013/1
N2 - The steroid hormone estradiol is suggested to play a protective role in intestinal injury during systemic inflammation (sepsis). Our aim was to determine the effects of specific estradiol receptor (ER-α and ER-ß) agonists on the intestinal microcirculation during experimental sepsis. Male and sham ovariectomized female rats were subjected to sham colon ascendens stent peritonitis (CASP), and they were compared to male and ovariectomized female rats underwent CASP and either estradiol receptor α (ER-α) agonist propyl pyrazole triol (PPT), estradiol receptor ß (ER-ß) agonist diarylpropiolnitrile (DPN), or vehicle treatment. Intravital microscopy was performed, which is sufficiently sensitive to measure changes in the functional capillary density (FCD) as well as the major steps in leukocyte recruitment (rolling and adhesion). The leukocyte extravasations were also quantified by using histological paraffin sections of formalin fixed intestine. We found that either DPN (ER-β) or PPT (ER-α) significantly reduced (P<0.05) sepsis-induced leukocyte-endothelial interaction (rolling, adherent leukocytes and neutrophil extravasations) and improved the intestinal muscular FCD. [PPT: Female; Leukocyte rolling (n/min): V3 3.7±0.7 vs 0.8±0.2, Leukocyte adhesion(n/mm2): V3 131.3±22.6 vs 57.2±13.5, Neutrophil extravasations (n/10000μm2): 3.1±0.7 vs 6 ±1. Male; Leukocyte adhesion (n/mm2): V1 154.8±19.2 vs 81.3±11.2, V3 115.5±23.1 vs 37.8±12]. [DPN: Female; neutrophil extravasations (n/10000μm2) 3.8±0.6 vs 6 ±1. Male; Leukocyte adhesion (n/mm2) V1 154.8±19.2 vs 70±10.5, V3 115.5±23.1 vs 52.8±9.6].Those results suggest that the observed effects of estradiol receptors on different phases of leukocytes recruitment with the improvement of the functional capillary density could partially explain the previous demonstrated salutary effects of estradiol on the intestinal microcirculation during sepsis. The observed activity of this class of compounds could open up a new avenue of research into the potential treatment of sepsis.
AB - The steroid hormone estradiol is suggested to play a protective role in intestinal injury during systemic inflammation (sepsis). Our aim was to determine the effects of specific estradiol receptor (ER-α and ER-ß) agonists on the intestinal microcirculation during experimental sepsis. Male and sham ovariectomized female rats were subjected to sham colon ascendens stent peritonitis (CASP), and they were compared to male and ovariectomized female rats underwent CASP and either estradiol receptor α (ER-α) agonist propyl pyrazole triol (PPT), estradiol receptor ß (ER-ß) agonist diarylpropiolnitrile (DPN), or vehicle treatment. Intravital microscopy was performed, which is sufficiently sensitive to measure changes in the functional capillary density (FCD) as well as the major steps in leukocyte recruitment (rolling and adhesion). The leukocyte extravasations were also quantified by using histological paraffin sections of formalin fixed intestine. We found that either DPN (ER-β) or PPT (ER-α) significantly reduced (P<0.05) sepsis-induced leukocyte-endothelial interaction (rolling, adherent leukocytes and neutrophil extravasations) and improved the intestinal muscular FCD. [PPT: Female; Leukocyte rolling (n/min): V3 3.7±0.7 vs 0.8±0.2, Leukocyte adhesion(n/mm2): V3 131.3±22.6 vs 57.2±13.5, Neutrophil extravasations (n/10000μm2): 3.1±0.7 vs 6 ±1. Male; Leukocyte adhesion (n/mm2): V1 154.8±19.2 vs 81.3±11.2, V3 115.5±23.1 vs 37.8±12]. [DPN: Female; neutrophil extravasations (n/10000μm2) 3.8±0.6 vs 6 ±1. Male; Leukocyte adhesion (n/mm2) V1 154.8±19.2 vs 70±10.5, V3 115.5±23.1 vs 52.8±9.6].Those results suggest that the observed effects of estradiol receptors on different phases of leukocytes recruitment with the improvement of the functional capillary density could partially explain the previous demonstrated salutary effects of estradiol on the intestinal microcirculation during sepsis. The observed activity of this class of compounds could open up a new avenue of research into the potential treatment of sepsis.
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U2 - 10.1016/j.mvr.2012.10.002
DO - 10.1016/j.mvr.2012.10.002
M3 - Article
C2 - 23063870
AN - SCOPUS:84871716027
SN - 0026-2862
VL - 85
SP - 118
EP - 127
JO - Microvascular Research
JF - Microvascular Research
IS - 1
ER -