Effects of isoproterenol on myocardial relaxation rate: influence of the level of load

Abstract

The present work was undertaken to test the hypothesis that the level of the load faced by the myocardium influences the effects of isoproterenol on relaxation rate. Responses to cumulative doses of isoproterenol (from 10(-10) to 10(-6) M) were studied in rat left ventricular papillary muscle stimulated 12 beats/min at 29 degrees C in 0.5 mM extracellular calcium and preloaded at initial muscle length corresponding to apex of length-active tension curve (Lmax; group 1, n = 20) or at 95% of Lmax (group 2, n = 9). A control group (group 3, n = 8) was studied every 15 min for 75 min. We measured maximum unloaded shortening velocity (Vmax), normalized positive and negative peak force derivatives (+dF and -dF, respectively) of the fully isometric twitch, and peak lengthening velocity of the isotonic twitch with preload only (Vlmax). In group 1, Vmax and +dF increased under 10(-10) and 10(-9) M isoproterenol, respectively, and -dF increased under 10(-9) M isoproterenol (115 +/- 13 vs. 96 +/- 12 mN.s-1.mm-2, P = 0.01). Conversely, Vlmax increased under 10(-7) M isoproterenol only (2.34 +/- 0.19 vs. 1.45 +/- 0.18 Lmax/s, P < 0.001). In group 2, both -dF and Vlmax increased under 10(-7) M isoproterenol only (P = 0.015 and 0.011, respectively). In group 3, -dF and Vlmax did not vary in time. Our results suggest a load-revealed (or length-revealed) difference in the dose dependence of the various biochemical processes involved in the effects of isoproterenol during myocardial relaxation.