Influence of ovariectomy on ventricular myocyte contraction in simulated diabetes.
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 (tau). Nitric oxide synthase (NOS) activity was also evaluated. OVX myocytes displayed a longer TR(90), slower +/- dL/dt, lower fluorescence intensity and higher tau (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 tau 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 tau), 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.
Hintz
K K
KK
Department of Pharmacology, Physiology and Therapeutics, University of North Dakota School of Medicine, Grand Forks, N. Dak 58203, USA.
Wold
L E
LE
Colligan
P B
PB
Scott
G I
GI
Lee
K J
KJ
Sowers
J R
JR
Ren
J
J
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D005260:Female; D005453:Fluorescence; D005947:Glucose / Q000008:administration & dosage; D006352:Heart Ventricles / Q000166:cytology*; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000502:physiology*; D010052:Ovariectomy; D010053:Ovary / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005947:Glucose; D002118:Calcium