title: Aromatase inhibition attenuates desflurane-induced preconditioning against acute myocardial infarction in male mouse heart in vivo.
abstract: The volatile anesthetic desflurane (DES) effectively reduces cardiac infarct size following experimental ischemia/reperfusion injury in the mouse heart. We hypothesized that endogenous estrogens play a role as mediators of desflurane-induced preconditioning against myocardial infarction. In this study, we tested the hypothesis that desflurane effects local estrogen synthesis by modulating enzyme aromatase expression and activity in the mouse heart. Aromatase metabolizes testosterone to 17β- estradiol (E2) and thereby significantly contributes to local estrogen synthesis. We tested aromatase effects in acute myocardial infarction model in male mice. The animals were randomized and subjected to four groups which were pre-treated with the selective aromatase inhibitor anastrozole (A group) and DES alone (DES group) or in combination (A+DES group) for 15 minutes prior to surgical intervention whereas the control group received 0.9% NaCl (CON group). All animals were subjected to 45 minutes ischemia following 180 minutes reperfusion. Anastrozole blocked DES induced preconditioning and increased infarct size compared to DES alone (37.94 ± 15.5% vs. 17.1 ± 3.62%) without affecting area at risk and systemic hemodynamic parameters following ischemia/reperfusion. Protein localization studies revealed that aromatase was abundant in the murine cardiovascular system with the highest expression levels in endothelial and smooth muscle cells. Desflurane application at pharmacological concentrations efficiently upregulated aromatase expression in vivo and in vitro. We conclude that desflurane efficiently regulates aromatase expression and activity which might lead to increased local estrogen synthesis and thus preserve cellular integrity and reduce cardiac damage in an acute myocardial infarction model.
authors.affiliation: Institute of Molecular and Translational Therapeutic Strategies, Hannover Medical School, MHH, Hannover, Germany. vjazbutyte@hotmail.com
authors.forename: Virginija
authors.initials: V
authors.lastname: Jazbutyte
authors.forename: Jan
authors.initials: J
authors.lastname: Stumpner
authors.forename: Andreas
authors.initials: A
authors.lastname: Redel
authors.forename: Johan M
authors.initials: JM
authors.lastname: Lorenzen
authors.forename: Norbert
authors.initials: N
authors.lastname: Roewer
authors.forename: Thomas
authors.initials: T
authors.lastname: Thum
authors.forename: Franz
authors.initials: F
authors.lastname: Kehl
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D001141:Aromatase / Q000235:genetics / Q000378:metabolism*; D047072:Aromatase Inhibitors / Q000009:adverse effects* / Q000494:pharmacology; D000077335:Desflurane; D005786:Gene Expression Regulation / Q000187:drug effects; D006439:Hemodynamics; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D007530:Isoflurane / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D021381:Protein Transport; D051381:Rats
chemical_list: D018685:Anesthetics, Inhalation; D047072:Aromatase Inhibitors; D000077335:Desflurane; D007530:Isoflurane; D001141:Aromatase