β-Adrenoceptor Stimulation-Mediated Preconditioning-like Cardioprotection in Perfused Rat Hearts

Abstract

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.

A Preliminary Study on the Cardioprotection of Acupuncture Pretreatment in Rats with Ischemia and Reperfusion: Involvement of Cardiac β-Adrenoceptors

“…Thus the repetitive EA pretreatment may also induce the desensitization of β-ARs via stimulating sympathetic activity to achieve the cardioprotective effects. In the present study, the cardioprotection of EA pretreatment was abolished by the administration of propranolol prior to each time of EA stimulation, which is in agreement with results in the previous studies on the cardioprotection of β-adrenergic preconditioning [6,21]. Accordingly, propranolol seems to temporarily "protect" 3.…”

“…Pretreatment with norepinephrine [4], a neurotransmitter of sympathetic endings in the heart, was shown to effectively mimic the protective effect of ischemic preconditioning on the heart subjected to ischemia and reperfusion. The protective effect induced by this pretreatment was associated with the induction of cardiac tolerance or adaptation to the subsequent overstimulation of β-adrenoceptors in cardiomyocytes [5] during the ischemia and reperfusion so as to attenuate the consequent cardiac impairment [6]. Acupuncture stimulation was reported to influence the activity of sympathetic nerves [7,8].…”

Ischemia/reperfusion injury is increased and cardioprotection by a postconditioning protocol is lost as cardiac hypertrophy develops in nandrolone treated rats

“…This aspect is very intriguing and has been attributed to the over-expression of β 2 adrenergic receptors, which are involved in the cardioprotection induced by PostC [37]. In fact, the release of catecholamines from sympathetic terminal nerves and β-AR stimulation play an important role in cardioprotection against necrosis and/or stunning [31,47,59,64]. We previously reported that the β 2 -AR antagonist, ICI-118.551, abolishes PostC-protection both in ND-and vehicle-pretreated hearts [37].…”

Antiarrhythmic Effect of Acupuncture Pretreatment in Rats Subjected to Simulative Global Ischemia and Reperfusion — Involvement of Adenylate Cyclase, Protein Kinase A, and L-Type Ca2+ Channel

“…Stimulating β 1 -AR with norepinephrine prior to ischemia can also mimic ischemic preconditioning to attenuate the ischemic myocardial injury [6,7]. AC, PKA, and L-type Ca 2+ channel are the important components of the β 1 -AR signaling pathway, and all of them were reported to contribute to the cardioprotection of ischemic preconditioning [34][35][36].…”

“…The wide use of β 1 -AR blockers in the treatment of arrhythmias [4] further confi rms the involvement of β 1 -AR in the genesis of cardiac arrhythmias. Similar to the cardioprotection produced by ischemic preconditioning, repetitive stimulation to either β 1 -AR or the components of its signaling pathway before myocardial ischemia and reperfusion (MIR) could attenuate the myocardial injury induced by the following prolonged ischemia and reperfusion [5][6][7]. Thus repetitive pretreatment with electro-acupuncture (EA), which was shown to excite the sympathetic nervous system, may also produce the cardioprotective effect via influencing β 1 -AR and/or its signaling pathway.…”