DIFFERENT PHARMACOLOGICAL RESPONSES OF ATRIUM AND VENTRICLE - STUDIESWITH HUMAN CARDIAC TISSUE

It has been recently reported that 5-hydroxytryptamine (5-HT) increase s 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 re sponses is specific for 5-HT or is also observed for other substances: calcitonin gene-related peptide (CGRP), angiotensin II, adenosine, so matostatin and acetylcholine. CGRP (10(-9) to 10(-7) M) and angiotensi n II(10(-9) to 10(-5) M) caused concentration-dependent increases in f orce 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 ventri cular trabeculae. Adenosine (10(-8) to 10(-5) M) and somatostatin (10( -8) to 10(-6) M) caused concentration-dependent negative inotropic eff ects on baseline atrial contractility (-54 +/- 17% and -51 +/- 25%, re spectively), but no response was found on baseline ventricular contrac tility. 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, consistin g 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 contra ction, acetylcholine (10(-9) to 10(-4) M) induced only a positive inot ropic 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 noradr enaline, acetylcholine reduced force of contraction in both tissues at 10(-3) M (atrium: - 14 +/- 4%, ventricle: -61 +/- 5%). The data indic ate that, in atrial tissue, force of contraction can be affected by ei ther positive or negative inotropic agents. However, in ventricular ti ssue only positive inotropic effects could be detected. Since atrial a nd ventricular tissues display different responses to the above biogen ic substances, a different mechanism of regulation of contractility se ems feasible.