Influence of ovariectomy on ventricular myocyte contraction in simulated diabetes

Abstract

We studied the effect of ovariectomy (OVX) on cardiac contraction in myocytes maintained under a ‘diabetes-simulated high-glucose’ environment. Female rats were ovariectomized or sham operated (SHAM) and kept for 6 weeks. Isolated myocytes were maintained in a diabetes-simulated high [glucose] medium (HG; 25.5 mM) for 24 h before mechanical properties were measured. Contractile indices analyzed included peak shortening (PS), time to PS (TPS), time to 90% relengthening (TR₉₀), maximal velocity of shortening and relengthening (± dL/dt), intracellular Ca²⁺ fura-2 fluorescence intensity and decay rate (τ). Nitric oxide synthase (NOS) activity was also evaluated. OVX myocytes displayed a longer TR₉₀, slower ± dL/dt, lower fluorescence intensity and higher τ (slower decay rate) when compared to SHAM myocytes. In the SHAM group, HG exerted diabetes-like contractile dysfunctions, including depressed PS, prolonged TR₉₀, reduced fluorescence intensity, higher τ and enhanced NOS activity when compared to myocytes maintained in low [glucose] medium (5.5 mM). Interestingly, the HG-induced mechanical alterations were significantly exaggerated (TPS, TR₉₀ and τ), reversed (PS and NOS) or lost (± dL/dt and fluorescence intensity) in the OVX group. These data suggest that ovarian hormones play a role in the regulation of cardiac contractile function, and may have potentially protective effects against diabetes-associated cardiac dysfunction.