title: Sex differences in the mechano-energetic effects of genistein on stunned rat and guinea pig hearts.
abstract: Although the phytoestrogen genistein (Gen) is considered protective in cardiovascular diseases, its direct effects on stunned hearts after transient ischemia-reperfusion (I/R) are unknown. This report studied the effects of 20 μmol/L Gen on the mechano-calorimetric behaviour during I/R of rat and guinea pig hearts to evaluate the energetics of Ca(2+) homeostasis. Isolated beating hearts were perfused with control Krebs solution inside a calorimeter with or without perfusion of Gen before a transient period of I/R. Left ventricular pressure development (P) and total heat rate (Ht) were continuously measured. At 37°C, Gen did not change post-ischemic contractile recovery (PICR), but it increased the relaxation rate. However, PICR was reduced in hearts of male rats and guinea pigs at 30°C. Total muscle economy (P/Ht) showed the same behaviour as P at each temperature. Inhibition of phosphatases with orthovanadate during Gen perfusion prevented a decrease in PICR in male rat hearts, suggesting that this effect is due to tyrosine kinase inhibition. Reperfusing ischemic hearts with 10 mmol/L caffeine-36 mmol/L Na(+)-Krebs induced contracture dependent on the sarcoreticular Ca(2+) content. Contracture relaxation depends on mitochondrial Ca(2+) uptake and Gen reduced the relaxation rate. Moreover, Gen prevented the increase in Rhod-2 fluorescence (free [Ca(2+)]m) of rat cardiomyocytes. In guinea pig hearts, Gen maintained ischemic preconditioning, but was reduced by 5-hydroxydecanoate, suggesting the participation of mitochondrial adenosine triphosphate (ATP)-dependent K channels. Results suggest that Gen acts on several mechanisms that regulate myocardial calcium homeostasis and energetics during I/R, which differ in a temperature- and sex-dependent manner.
authors.affiliation: Experimental Pharmacology Group (GFEYEC), Department of Biological Sciences, School of Exactas Sciences, National University of La Plata, La Plata, Argentina.
authors.forename: Germán A
authors.initials: GA
authors.lastname: Colareda
authors.affiliation: Experimental Pharmacology Group (GFEYEC), Department of Biological Sciences, School of Exactas Sciences, National University of La Plata, La Plata, Argentina.|National Council of Scientific and Technical Research (CONICET), La Plata, Argentina.
authors.forename: María I
authors.initials: MI
authors.lastname: Ragone
authors.affiliation: Experimental Pharmacology Group (GFEYEC), Department of Biological Sciences, School of Exactas Sciences, National University of La Plata, La Plata, Argentina.
authors.forename: Alicia E
authors.initials: AE
authors.lastname: Consolini
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D017682:Myocardial Stunning / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D051381:Rats; D015427:Reperfusion Injury / Q000150:complications; D012727:Sex Characteristics; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D019833:Genistein; D002118:Calcium
keywords: calorimetry; genistein; heart; ischemia/reperfusion; phytoestrogen