UNASSIGNED: The alpha2-adrenergic receptor agonist @entity6948 ( @entity9170 ) is a sedative medication used by anesthesiologists. @entity9170 protects the heart against @entity63 -reperfusion (IR) and can also act as a preconditioning mimetic. The mechanisms involved in @entity9170 -dependent cardiac preconditioning, and whether this action occurs directly or indirectly on cardiomyocytes, still remain unclear. The endothelial @entity842 synthase (eNOS)/ @entity842 (NO) signaling pathway and endothelial cells are known to play key roles in cardioprotection against @entity5721 . Therefore, the aims of this work were to evaluate whether the eNOS/NO pathway mediates the pharmacological cardiac effect of @entity9170 , and whether endothelial cells are required in this cardioprotective action. Isolated adult @entity35 hearts were treated with @entity9170 (10nM) for 25min and the dimerization of eNOS and production of NO were measured. Hearts were then subjected to global IR (30/120min) and the role of the eNOS/NO pathway was evaluated. @entity9170 promoted the activation of eNOS and production of NO. @entity9170 reduced the @entity1188 size and improved the left ventricle function recovery, but this effect was reversed when @entity9170 was co-administered with inhibitors of the eNOS/NO/PKG pathway. In addition, @entity9170 was unable to reduce cell @entity204 in isolated adult @entity35 cardiomyocytes subjected to simulated IR. Cardiomyocyte @entity204 was attenuated by co-culturing them with endothelial cells pre-treated with @entity9170 . In summary, our results show that @entity9170 triggers cardiac protection by activating the eNOS/NO signaling pathway. This pharmacological effect of @entity9170 requires its interaction with the endothelium.

@entity6948 protects the heart against XXXX -reperfusion injury by an endothelial eNOS/NO dependent mechanism.

@entity5721 :: ('MESH:D015427', 'Disease') :: ['IR injury'] @entity9170 :: ('D003907', 'Chemical') :: ['Dex'] @entity63 :: ('MESH:D007511', 'Disease') :: ['ischemia'] @entity1188 :: ('MESH:D007238', 'Disease') :: ['infarct'] @entity842 :: ('MESH:D009569', 'Chemical') :: ['nitric oxide'] @entity35 :: ('10116', 'Species') :: ['rat'] @entity6948 :: ('MESH:D020927', 'Chemical') :: ['Dexmedetomidine'] @entity204 :: ('MESH:D003643', 'Disease') :: ['death']
@entity63 :: (MESH:D007511,Disease) :: ['ischemia']
