Pharmacological blockade of sarcoplasmic reticulum induces a negative lusitropic effect.

The relaxation and the inter-beat mechanical tension are termed lusitropic functions. It is generally assumed that they are primarily determined by Ca(2+) homeostasis of cardiac cell and by interactions of Ca(2+) with the contractile machinery. In the present study we studied the effects of various pharmacological interventions on the excitation-contraction coupling in right ventricular papillary muscles of adult rabbits at various stimulation rates. The maximal force of isometric contraction (MG, a.u.), the time to peak of isometric contraction (TTP, ms), the maximal speed of relaxation (dF/dt(relax)), the diastolic tension (DT, a.u.) and the total tension (MG+DT, a.u.) were measured. To affect excitation-contraction coupling, caffeine (5 mmol x l(-1)), ryanodine (1 micromol x l(-1)) and dantrolene sodium (50 micromol x l(-1)) were used. Whereas caffeine and ryanodine elicited a pronounced negative lusitropic effect, the effect of dantrolene was less dramatic with preserved frequency dependence. The results indicate that the key element for affecting the lusitropic functions is the ryanodine receptor of the sarcoplasmic reticulum (SR). The lusitropic effects of dantrolene, that affects cardiac excitation-contraction coupling but only minimally the ryanodine receptors of SR, were considerably less pronounced. The findings agree with the assumption that the lusitropic disturbances are closely related to the defects of SR ryanodine receptors of cardiac myocytes.