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).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, Cardiovascular Research Institute COEUR, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, Netherlands.
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D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D006325:Heart Atria / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects*; D013004:Somatostatin / Q000494:pharmacology
D002316:Cardiotonic Agents; D013004:Somatostatin; D015740:Calcitonin Gene-Related Peptide; D000241:Adenosine; D000109:Acetylcholine