Comparison of the positive inotropic effects of serotonin, histamine, angiotensin II, endothelin and isoprenaline in the isolated human right atrium.
The receptor systems through which serotonin (5-HT), histamine, angiotensin II and endothelin increase the force of contraction were studied in isolated right atria from patients without apparent heart failure. All agonists increased the atrial force of contraction in a concentration-dependent manner; maximal effects, however, were significantly less than those evoked by isoprenaline or Ca2+. 5-HT and histamine, but not angiotensin II and endothelin, activated adenylate cyclase, whereas endothelin and angiotensin II stimulated inositol phosphate generation. Experiments with subtype-selective antagonists revealed that histamine effects were mediated by H2-receptors (sensitive to ranitidine), 5-HT-effects by 5-HT4-receptors (sensitive to SDZ 205-557) and angiotensin II effects by AT1-receptors (sensitive to losartan). We conclude that in human right atria the force of contraction can be increased by cyclic AMP-dependent (histamine, 5-HT) and -independent (angiotensin II, endothelin) pathways. Compared to beta-adrenoceptors, however, all other receptor systems increase the force of contraction only submaximally indicating that the beta-adrenoceptor pathway is the most important physiological mechanism to regulate force of contraction and/or heart rate in the human heart.
Zerkowski
H R
HR
Abteilung Thorax- und Kardiovaskuläre Chirurgie, Universitätsklinikum Essen, Federal Republic of Germany.
Broede
A
A
Kunde
K
K
Hillemann
S
S
Schäfer
E
E
Vogelsang
M
M
Michel
M C
MC
Brodde
O E
OE
D000262:Adenylyl Cyclases / Q000187:drug effects; D000328:Adult; D000368:Aged; D000804:Angiotensin II / Q000494:pharmacology; D001685:Biological Factors / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology; D005260:Female; D006325:Heart Atria / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology; D013268:Stimulation, Chemical
D001685:Biological Factors; D002316:Cardiotonic Agents; D016232:Endothelins; D007295:Inositol Phosphates; D011956:Receptors, Cell Surface; D000804:Angiotensin II; D012701:Serotonin; D006632:Histamine; D000262:Adenylyl Cyclases; D007545:Isoproterenol