Differential effects of caffeine on skinned fibers from control and hypertrophied ferret hearts.

The effects of caffeine on the mechanical properties of detergent-skinned fibers from control and pressure-overloaded ferret hearts have been compared. Right ventricle hypertrophy was studied 6 wk after pulmonary artery ligation, an intervention that increased the right ventricular weight-body weight ratio by 60%. Although no changes were observed in the Ca sensitivity of contraction between control [pCa for one-half-maximal activation (pCa50) = 5.80 +/- 0.05] and hypertrophied (pCa50 = 5.85 +/- 0.02) muscles, the leftward shift of the force-pCa relationship induced by caffeine was more pronounced in hypertrophied fibers than in control; pCa50, was 5.86 +/- 0.02, 5.94 +/- 0.01, 6.03 +/- 0.01 in control and 5.97 +/- 0.03, 6.10 +/- 0.03, 6.24 +/- 0.01 in control and 5.97 +/- 0.03, 6.10 +/- 0.03, 6.24 +/- 0.03 in hypertrophied fibers for 2, 5, 10 mM caffeine, respectively. This was accompanied in the hypertrophied muscles by a decrease in the Hill coefficient. On the other hand, maximal force was not affected by 10 mM caffeine. From these results it is possible that the site of action of caffeine in myofibrillar proteins is the thin filament. The increased responsiveness of hypertrophied fibers to caffeine may be mediated by a pressure overload-induced change in the thin filament regulatory proteins. Moreover, inotropic agents may act differently in hypertrophied than in control myocardium.