Estradiol receptors agonists induced effects in rat intestinal microcirculation during sepsis

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-alpha and ER-beta) 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 alpha (ER-alpha) agonist propyl pyrazole triol (PPT), estradiol receptor beta (ER-beta) 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-beta) or PPT (ER-alpha) 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): V-3 3.7 +/- 0.7 vs 0.8 +/- 0.2, Leukocyte adhesion(n/mm(2)): V-3 131.3 +/- 22.6 vs 57.2 +/- 13.5, Neutrophil extravasations (n/10000 mu m(2)): 3.1 +/- 0.7 vs 6 +/- 1. Male; Leukocyte adhesion (n/mm(2)): V-1 154.8 +/- 19.2 vs 81.3 +/- 11.2, V-3 115.5 +/- 23.1 vs 37.8 +/- 12]. [DPN: Female; neutrophil extravasations (n/10000 mu m(2)) 3.8 +/- 0.6 vs 6 +/- 1. Male; Leukocyte adhesion (n/mm(2)) V-1 154.8 +/- 192 vs 70 +/- 10.5, V-3 115.5 +/- 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. (C) 2012 Elsevier Inc. All rights reserved.