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Ischemic Tolerance and Conventional Preconditioning are Impaired by Chronic β 1 ‐Blockade
Author(s) -
See Hoe Louise,
Schilling Jan,
Busija Anna,
Roth David,
Patel Hemal,
Peart Jason
Publication year - 2015
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.29.1_supplement.635.1
Subject(s) - atenolol , medicine , blockade , ischemic preconditioning , ischemia , cardiology , placebo , pharmacology , anesthesia , blood pressure , receptor , pathology , alternative medicine
β‐adrenoceptor (β‐AR) antagonists are commonly prescribed to ischemic heart disease (IHD) patients. In addition to age and disease, β‐blockade may impair efficacies of cardioprotective approaches. We assessed the effects of chronic β 1 ‐AR antagonism on myocardial tolerance to ischemia‐reperfusion (I/R), and the efficacies of ischemic preconditioning (IPC) and sustained ligand‐activated preconditioning (SLP) in murine hearts. Male C57/Bl6 mice received β 1 ‐AR‐blocker atenolol for 4 weeks (0.5 g/L in drinking water) before subcutaneous implantation of morphine (SLP) or placebo pellets 5 days prior to analysis of ischemic outcomes ex vivo . Atenolol significantly reduced i n vivo heart rate and responses to isoproterenol in all groups, an effect exaggerated with SLP. Control (placebo) hearts exhibited significant post‐ischemic contractile depression, with ~50% recovery of developed pressure, significant diastolic dysfunction and lactate dehydrogenase (LDH) release, effects inflated by chronic β 1 ‐AR blockade with atenolol. Both IPC and SLP significantly improved post‐ischemic outcomes and LDH release (~50% improvement). Interestingly, IPC protection was negated by chronic atenolol treatment, yet SLP‐mediated protection persisted irrespective of β 1 ‐AR blockade. Western blot analysis suggests Src phosphorylation with IPC was blocked by atenolol. Data indicate that chronic β 1 ‐AR blockade impairs intrinsic ischemic tolerance and classical preconditioning responses whereas novel SLP retains protective efficacy likely due to distinct signaling mechanisms.