Beta-adrenoceptor stimulation-mediated preconditioning-like cardioprotection in perfused rat hearts.
To determine whether adrenergic stimulation induces preconditioning-like cardioprotection, rat hearts were perfused for 2 min with either norepinephrine, phenylephrine, or isoproterenol followed by 10-min drug-free perfusion. Then the hearts were subjected to 40-min ischemia and 30-min reperfusion. Little recovery of left ventricular developed pressure (LVDP) and loss of the myocardial creatine kinase (CK) during reperfusion were observed in the drug-untreated heart. Preperfusion with norepinephrine (0.25 microM) or isoproterenol (0.25 microM), but not phenylephrine (10 microM), resulted in a better recovery of LVDP in the postischemic reperfused heart and a reduction in CK release during reperfusion. A similar improvement of postischemic cardiac contractile dysfunction and CK loss was seen in the heart subjected to 5-min ischemia followed by 5-min reperfusion (ischemic preconditioning) before the prolonged period of ischemia/reperfusion. Pretreatment with timolol, a beta-adrenoceptor blocker, abolished the protective effect of norepinephrine, whereas pretreatment with bunazosin, an alpha 1-adrenoceptor blocker, did not affect the protective effect of isoproterenol. The results suggest that a brief period of stimulation of cardiac beta-adrenoceptor exerts the preconditioning-mimetic protective effect against postischemic contractile dysfunction in perfused rat hearts.
Nasa
Y
Y
Department of Pharmacology, Tokyo University of Pharmacy and Life Science, Japan.
Yabe
K
K
Takeo
S
S
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003402:Creatine Kinase / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000503:physiopathology; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013999:Timolol / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011799:Quinazolines; D010656:Phenylephrine; D013999:Timolol; C018176:bunazosin; D003402:Creatine Kinase; D007545:Isoproterenol; D009638:Norepinephrine