Aging: inotropic effects of Bay K-8644 and nifedipine on rat cardiac muscle

Abstract

Inotropic effects of Bay K-8644, nifedipine, isoproterenol and extracellular calcium (Ca o 2+) were examined in right ventricular strips, papillary muscle and left atria isolated from 4, 14 and 25 month old, male F344 rats. Under the experimental conditions used (37°C, 1.4 mM Ca o 2+ and 4 Hz), control developed tension (expressed per mg wet weight) increased with age in right ventricular strips and papillary muscle, but decreased in left atria. The maximal positive inotropic response to Bay K-8644 was diminished with age in right ventricular strips and papillary muscle (but not left atria), while the negative inotropic action of nifedipine was not affected in any of the three tissues. Age decreased the inotropic efficacy of isoproterenol in right ventricular strips and papillary muscle (not left atria), had no effect on the efficacy of Ca o 2+ in right ventricular strips and left atria, but diminished the maximum response to Ca o 2+ in papillary muscle. K d and B max values for [ 3H]nitrendipine binding were not significantly different in the three age groups. These data suggest: (1) that age-related changes in basal contractility and inotropic responsiveness differ in atrial and ventricular muscle; and (2) that these changes may result from alterations in excitation-contraction coupling which are not mediated by changes in Ca 2+ channel density.