Myocardial cross-bridge kinetics in transition to failure in Dahl salt-sensitive rats.
The role of altered cross-bridge kinetics during the transition from cardiac hypertrophy to failure is poorly defined. We examined this in Dahl salt-sensitive (DS) rats, which develop hypertrophy and failure when fed a high-salt diet (HS). DS rats fed a low-salt diet were controls. Serial echocardiography disclosed compensated hypertrophy at 6 wk of HS, followed by progressive dilatation and impaired function. Mechanical properties of skinned left ventricular papillary muscle strips were analyzed at 6 wk of HS and then during failure (12 wk HS) by applying small amplitude (0.125%) length perturbations over a range of calcium concentrations. No differences in isometric tension-calcium relations or cross-bridge cycling kinetics or mechanical function were found at 6 wk. In contrast, 12 wk HS strips exhibited increased calcium sensitivity of isometric tension, decreased frequency of minimal dynamic stiffness, and a decreased range of frequencies over which cross bridges produce work and power. Thus the transition from hypertrophy to heart failure in DS rats is characterized by major changes in cross-bridge cycling kinetics and mechanical performance.
McCurdy
D T
DT
Cardiology Unit, University of Vermont Medical School, Burlington, Vermont 05405, USA.
Palmer
B M
BM
Maughan
D W
DW
LeWinter
M M
MM
D000220:Adaptation, Biological; D000818:Animals; D001683:Biological Clocks; D001835:Body Weight; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D006332:Cardiomegaly / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D004452:Echocardiography; D004548:Elasticity; D006333:Heart Failure / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology*; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology*; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D009929:Organ Size; D010210:Papillary Muscles / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D020303:Rats, Inbred Dahl; D017673:Sodium Chloride, Dietary; D013314:Stress, Mechanical; D015996:Survival Rate
D017673:Sodium Chloride, Dietary; D002118:Calcium