Decreased myocyte tension development and calcium responsiveness in rat right ventricular pressure overload.
BACKGROUND
The contractile dysfunction observed in end-stage myocardial hypertrophy has at its base an abnormality in myocyte function. However, whether depressed contractile function is related to an alteration in contractile protein function is presently unknown.


RESULTS
Contractile force, tension, and calcium responsiveness were measured in single-skinned myocytes isolated from rats with right ventricular hypertrophy (RVH) and control rats. RVH was induced by pulmonary artery constriction for 36 weeks and was associated with significant myocyte hypertrophy. Myocytes were attached to micropipettes that extended from a force transducer and motor. Isometric force was measured over a wide range of calcium concentrations at two sarcomere lengths (SLs). Maximal force was increased in the RVH group: 1.20 +/- 0.10 versus 1.62 +/- 0.13 mg at SL = 2.0 microns and 1.33 +/- 0.10 versus 1.84 +/- 0.15 mg at SL = 2.3 microns (P < .05). Maximal tension, however, was reduced in the RVH group: 24.3 +/- 1.91 versus 37.5 +/- 2.92 mN/mm2 at SL = 2.0 microns and 27.4 +/- 1.78 versus 41.8 +/- 3.19 mN/mm2 at SL = 2.3 microns (P < .01). The concentration of calcium ions required for half-maximal activation was increased in the RVH group: 2.64 +/- 0.13 versus 3.47 +/- 0.22 mumol/L at SL = 2.0 microns and 2.23 +/- 0.15 versus 2.86 +/- 0.18 mumol/L at SL = 2.3 microns (P < .01). The slope of the force-calcium relationship (Hill coefficient) was decreased in the RVH group at SL = 2.0 microns (4.3 +/- 0.4 versus 3.1 +/- 0.2, P = .04) but not at SL = 2.3 microns (3.8 +/- 0.2 versus 3.6 +/- 0.2, P = NS).


CONCLUSIONS
These results suggest that the depressed cardiac function of end-stage myocardial hypertrophy may be due, in part, to altered contractile protein function.
Fan
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Section on Cardiology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157-1045, USA.
Wannenburg
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de Tombe
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D000818:Animals; D002118:Calcium / Q000502:physiology*; D003250:Constriction; D006973:Hypertension / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000473:pathology; D011651:Pulmonary Artery; D051381:Rats; D017207:Rats, Sprague-Dawley; D016278:Ventricular Function, Right
D002118:Calcium