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Pharmacological modulation of b-adrenoceptors as a new cardioprotective strategy for therapy of myocardial dysfunction induced by ischemia and reperfusion1 1 Research performed at Laboratório de Farmacologia Autonômica e Cardiovascular (LabFAC), Department of Pharmacology, Universidade Federal de São Paulo (UNIFESP), Brazil. Part of PhD degree thesis, Postgraduate Program in Pharmacology. Tutor: Prof. Dr. Afonso Caricati-Neto.

Abstract

Purpose:

To evaluate the cardioprotective response of the pharmacological modulation of β-adrenergic receptors (β-AR) in animal model of cardiac ischemia and reperfusion (CIR), in spontaneously hypertensive (SHR) and normotensive (NWR) rats.

Methods:

CIR was induced by the occlusion of left anterior descendent coronary artery (10 min) and reperfusion (75 min). The SHR was treated with β-AR antagonist atenolol (AT, 10 mg/kg, IV) 5 min before CIR, and NWR were treated with β-AR agonist isoproterenol (ISO, 0.5 mg/kg, IV) 5 min before CIR.

Results:

The treatment with AT increased the incidence of VA, AVB and LET in SHR, suggesting that spontaneous cardioprotection in hypertensive animals was abolished by blockade of β-AR. In contrast, the treatment with ISO significantly reduced the incidence of ventricular arrhythmia, atrioventricular blockade and lethality in NWR (30%, 20% and 20%, respectively), suggesting that the activation of β-AR stimulate cardioprotection in normotensive animals. Serum CK-MB were higher in SHR/CIR and NWR/CIR compared to respective SHAM group (not altered by treatment with AT or ISO).

Conclusion:

The pharmacological modulation of β-AR could be a new cardioprotective strategy for the therapy of myocardial dysfunctions induced by CIR related to cardiac surgery and cardiovascular diseases.

Key words:
Cardiovascular Diseases; Myocardial Ischemia; Reperfusion; Receptors, Adrenergic; Drug Therapy; Rats

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