Single acute stress-induced progesterone and ovariectomy alter cardiomyocyte contractile function in female rats

Judit Kalász, Eniko Pásztor Tóth, Beáta Bódi, Miklós Fagyas, Attila Tóth, Bhattoa Harjit Pal, Sándor G. Vári, Marta Balog, Senka Blažetić, Marija Heffer, Zoltán Papp, Attila Borbély

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Abstract

Aim: To assess how ovarian-derived sex hormones (in particular progesterone) modify the effects of single acute stress on the mechanical and biochemical properties of left ventricular cardiomyocytes in the rat. Methods: Non-ovariectomized (control, n = 8) and ovariectomized (OVX, n = 8) female rats were kept under normal conditions or were exposed to stress (control-S, n = 8 and OVX-S, n = 8). Serum progesterone levels were measured using a chemiluminescent immunoassay. Left ventricular myocardial samples were used for isometric force measurements and protein analysis. Ca2+-dependent active force (Factive), Ca2+-independent passive force (Fpassive), and Ca2+-sensitivity of force production were determined in single, mechanically isolated, permeabilized cardiomyocytes. Stress- and ovariectomy-induced alterations in myofilament proteins (myosin-binding protein C [MyBP-C], troponin I [TnI], and titin) were analyzed by sodium dodecyl sulfate gel electrophoresis using protein and phosphoprotein stainings. Results: Serum progesterone levels were significantly increased in stressed rats (control-S, 35.6 ± 4.8 ng/mL and OVX-S, 21.9 ± 4.0 ng/mL) compared to control (10 ± 2.9 ng/mL) and OVX (2.8 ± 0.5 ng/mL) groups. Factive was higher in the OVX groups (OVX, 25.9 ± 3.4 kN/m2 and OVX-S, 26.3 ± 3.0 kN/m2) than in control groups (control, 16.4 ± 1.2 kN/m2 and control-S, 14.4 ± 0.9 kN/m2). Regarding the potential molecular mechanisms, Factive correlated with MyBP-C phosphorylation, while myofilament Ca2+-sensitivity inversely correlated with serum progesterone levels when the mean values were plotted for all animal groups. Fpassive was unaffected by any treatment. Conclusion: Stress increases ovary-independent synthesis and release of progesterone, which may regulate Ca2+-sensitivity of force production in left ventricular cardiomyocytes. Stress and female hormones differently alter Ca2+- dependent cardiomyocyte contractile force production, which may have pathophysiological importance during stress conditions affecting postmenopausal women.

Original languageEnglish
Pages (from-to)239-249
Number of pages11
JournalCroatian Medical Journal
Volume55
Issue number3
DOIs
Publication statusPublished - Jun 2014

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ASJC Scopus subject areas

  • Medicine(all)

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