Journal of molecular and cellular cardiology
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J. Mol. Cell. Cardiol. · Aug 2001
Comparative StudyBW373U86, a delta opioid agonist, partially mediates delayed cardioprotection via a free radical mechanism that is independent of opioid receptor stimulation.
Opioids have been shown to produce both an early and delayed phase of cardioprotection; however, the signaling pathways involved, particularly in the delayed response, have not been well defined. Therefore, we investigated the potential of BW373U86 (BW), a potent delta opioid agonist, to produce delayed cardioprotection and characterized the role of opioid receptors and oxygen-derived free radicals (OFRs) in this delayed response. All rats underwent 30 min of ischemia followed by 2 h of reperfusion. ⋯ This protection was blocked by pretreatment with 2-MPG (42+/-4%, P<0.001). These data suggest that BW and TAN-67 mediate delayed cardioprotection via a free radical mechanism that appears to be only partially dependent on delta opioid receptor stimulation. Furthermore, it is the early burst in OFRs that is crucial to initiating the protective effect.
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J. Mol. Cell. Cardiol. · Aug 2001
Comparative StudyCyclosporine reduces left ventricular mass with chronic aortic banding in mice, which could be due to apoptosis and fibrosis.
A tacit assumption in studies of left ventricular (LV) hypertrophy is that left ventricular/body weight (LV/BW) reflects the extent of myocyte hypertrophy. The goal of the current investigation was to determine if there was another explanation for the reduced LV/BW observed after inhibiting calcineurin with cyclosporine during the development of pressure overload LV hypertrophy as compared with animals that did not receive cyclosporine. Accordingly, we examined the prevalence of fibrosis and apoptosis and measured cell size in the hearts from mice at 1 and 3 weeks after transverse aortic banding with and without chronic cyclosporine. ⋯ Immunoblotting demonstrated a decrease in the phosphorylation of Akt and Bad, and also Bcl-2 levels were reduced in aortic banded cyclosporine treated animals at 7 days compared with aortic banded vehicle treated animals. These proteins protect against apoptosis, and support the concept that cyclosporine inhibited the calcineurin pathway, resulting in enhanced apoptosis. Thus, the decrease in LV/BW in the aortic banded cyclosporine treated animals actually may be due, at least in part, to cell loss and death, as reflected by the enhanced fibrosis and apoptosis and the focal iron deposits in myocytes.