DIFFERENT PHARMACOLOGICAL RESPONSES OF ATRIUM AND VENTRICLE - STUDIES WITH HUMAN CARDIAC TISSUE

It has been recently reported that 5-hydroxytryptamine (5-HT) increases force of contraction in atrial tissue but not in ventricular tissue. In the present study with trabeculae obtained from non-diseased human hearts, we investigated whether this difference in the contractile responses is specific for 5-HT or is also observed for other substances: calcitonin gene-related peptide (CGRP), angiotensin II, adenosine, somatostatin and acetylcholine. CGRP (10(-9) to 10(-7) M) and angiotensin II(10(-9) to 10(-5) M) caused concentration-dependent increases in force of contraction in atrial trabeculae (up to 36 +/- 8% and 42 +/- 8% of the response to 10(-5) M noradrenaline, respectively). Similar to 5-HT, no effects were observed with CGRP and angiotensin II in ventricular trabeculae. Adenosine (10(-8) to 10(-5) M) and somatostatin (10(-8) to 10(-6) M) caused concentration-dependent negative inotropic effects on baseline atrial contractility (-54 +/- 17% and -51 +/- 25%, respectively), but no response was found on baseline ventricular contractility. Adenosine, but not somatostatin, reduced force of contraction after pre-stimulation with 10(-5) M noradrenaline in atrial tissue and, to a lesser extent, in ventricular tissue. Acetylcholine exhibited a biphasic concentration-response curve in the atrial tissue, consisting of an initial negative inotropic response (10(-9) to 10(-7) M, from 120 +/- 41 mg at baseline to 48 +/- 16 mg at 10(-7) M), followed by a positive inotropic response (10(-6) to 10(-3) M, from 48 +/- 16 mg at 10(-7) M to 77 +/- 15 mg). On the baseline ventricular force of contraction, acetylcholine (10(-9) to 10(-4) M) induced only a positive inotropic effect, starting at 10(-9) M (from 252 +/- 65 mg at baseline to 353 +/- 71 mg at 10(-4) M). After pre-stimulation with 10(-5) M noradrenaline, acetylcholine reduced force of contraction in both tissues at 10(-3) M (atrium: - 14 +/- 4%, ventricle: -61 +/- 5%). The data indicate that, in atrial tissue, force of contraction can be affected by either positive or negative inotropic agents. However, in ventricular tissue only positive inotropic effects could be detected. Since atrial and ventricular tissues display different responses to the above biogenic substances, a different mechanism of regulation of contractility seems feasible.