Chronotropic and inotropic response to tyramine in the intact and sympathectomized albino rats

University of Bristol (2005) J Physiol 567P, PC43

Poster Communications: Chronotropic and inotropic response to tyramine in the intact and sympathectomized albino rats

Sviglerova, Jitka; Kuncova, Jitka; Slavikova, Jana;

1. Dept. of Physiology, Charles University, Faculty of Medicine, Plzen, Czech Republic.

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The present study was designed to get better insight into the relationship between the developing cardiac sympathetic innervation and myocardial function. We studied the effect of tyramine on contractile properties and heart rate in control and sympathectomized albino rats from birth till adulthood. We evaluated concentrations of noradrenaline (NA) and neuropeptide Y (NPY) in the cardiac tissue. The chemical sympathectomy was performed by repeated injections of 6-hydroxydopamine (6-OHDA) immediately after birth. Experiments were carried out in 10, 20, 40 and 60-day-old animals (n=6 for control groups and n=5 for 6-OHDA groups). The contraction force (CF) of the right ventricular papillary muscle and the heart rate of the isolated right heart atrium were measured in the Tyrode solution without and with tyramine (concentrations from10-7 to 10-4 mmol/l). Atrial and ventricular concentrations of NA and NPY were measured by radioimmunoassay diagnostic kits. All procedures were performed according to current EU legislation and local guidelines. Statistical analysis was performed using one-way ANOVA (P<0.05) and post hoc Student’s unpaired t test with Bonferroni correction. In control rats, tyramine had positive inotropic and chronotropic effects, both effects of tyramine were inhibited by non-selective β-adrenoreceptor blocker metipranolol. Sympathectomy significantly lowered CF (P<0.05) in all followed groups except 60-day-old animals where no difference in CF between intact and sympathectomized rats was observed. In contrast to controls, both tyramine and metipranolol had no effect on the heart rate and CF in 6-OHDA rats of any age groups. This result is consistent with NA concentration in sympathectomized rats, which reached maximally 5% of control values (P<0.05) in all cardiac compartments and did not change in the whole course of experiment. No effect of tyramine and decrease in NA concentrations reflect the long-termed destructive effect of 6-OHDA on the cardiac sympathetic nerves. NPY is known to be co-secreted with NA from sympathetic postganglionic fibers. Moreover NPY is located in the intracardiac ganglia (1). It was found that NPY contributes to the increase in L-type calcium current density (2) and rapidly enhances calcium transients and sparks (3) in the rat ventricle. In our experiments, NPY concentration in the cardiac atria and ventricles of the younger (40 days and less) denervated rats was significantly (P<0.05) lower than in control ones. In older 6-OHDA rats (more than 40 days), NPY concentrations increased and were comparable with control values. Our results suggested that although sympathetic postganglionic fibers are destructed by 6-OHDA, NPY from preserved intracardiac ganglia might be able to improve contractile performance of the papillary muscle probably by influence of calcium metabolism in ventricular myocytes.



Where applicable, experiments conform with Society ethical requirements.

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