Abrogated cardioprotective effect of ischemic preconditioning in ovariectomized rat heart.
BACKGROUND
Ischemic heart disease is the leading cause of death in postmenopausal women. The expression of caveolin, a membrane protein and a negative regulator of nitric oxide (NO), increases after menopause. The present study was designed to determine the effect of daidzein (DDZ), a phytoestrogen in attenuated cardioprotective effect of ischemic preconditioning (IPC) in ovariectomized rat heart.


METHODS
Heart was isolated from ovariectomized rat and mounted on Langendorff's apparatus, subjected to 30 min ischemia and 120 min reperfusion. IPC was mediated by four cycles of 5 min ischemia and 5 min reperfusion. The infarct size was estimated using triphenyltetrazolium chloride stain, and coronary effluent was analyzed for lactate dehydrogenase and creatine kinase MB (CK-MB) release to assess the degree of myocardial injury. The release of NO was estimated indirectly by measuring the release of nitrite in coronary effluent.


RESULTS
IPC-induced cardioprotection was significantly attenuated in ovariectomized rats as compared to normal rats, which was restored by treatment of DDZ, a caveolin inhibitor (0.2 mg/kg subcutaneously) for 1 week. However, this observed cardioprotection was significantly attenuated by perfusion of l-nitroarginine methyl ester, an endothelial nitric oxide synthase (eNOS) inhibitor (100 µM/L) and glibenclamide, an adenosine triphosphate-sensitive potassium ion channel blocker (10 µM/L) alone or in combination, noted in terms of increase in myocardial infarct size, release of LDH and CK-MB, and also decrease in the release of NO.


CONCLUSIONS
Thus, it is suggested that DDZ restores the attenuated cardioprotective effect in ovariectomized rat heart, which may be due to downregulation of caveolin and subsequent increase in the activity of eNOS.
Department of Pharmacology, Institute of Pharmaceutical Research, GLA University, Mathura, Uttar Pradesh, India.
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Goyal
Department of Pharmacology, Institute of Pharmaceutical Research, GLA University, Mathura, Uttar Pradesh, India.
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Semwal
Department of Pharmacology, Institute of Pharmaceutical Research, GLA University, Mathura, Uttar Pradesh, India hnyadav@gmail.com.
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Yadav
D000818:Animals; D051242:Caveolin 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D052279:Creatine Kinase, MB Form / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D007529:Isoflavones / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009203:Myocardial Infarction / Q000378:metabolism* / Q000517:prevention & control*; D009573:Nitrites / Q000378:metabolism; D010052:Ovariectomy; D048789:Phytoestrogens / Q000494:pharmacology; D017208:Rats, Wistar
D051242:Caveolin 1; D007529:Isoflavones; D009573:Nitrites; D048789:Phytoestrogens; C004742:daidzein; D007770:L-Lactate Dehydrogenase; D052279:Creatine Kinase, MB Form
Ovariectomy; caveolin; daidzein; ischemic preconditioning; nitric oxide