The indirect negative inotropic effect of carbachol in beta1-adrenoceptor antagonist-treated human right atria.
To find out whether indirect negative inotropic effects of carbachol (i.e. decreases in force of contraction that had been stimulated by cyclic AMP-increasing agents) might differ dependent on the agonist employed to increase contractile force in isolated human right atrium, we studied effects of carbachol on atria prestimulated with noradrenaline, terbutaline, histamine and serotonin. All four agonists increased right atrial adenylyl cyclase activity and contractile force, whereby increases for terbutaline, histamine and serotonin, but not for noradrenaline, were significantly larger in right atria from beta(1)-adrenoceptor antagonist-treated vs. non-beta(1)-adrenoceptor antagonist-treated patients. Carbachol (10(-8)-10(-3) M) concentration-dependently decreased agonist-stimulated contractile force: maximum decrease was not significantly different within the four agonists. pD(2) values for carbachol, however, were higher in atria from non-beta(1)-adrenoceptor antagonist-treated vs. beta(1)-adrenoceptor antagonist-treated patients.We conclude that, in isolated human right atria, carbachol-induced indirect negative inotropic effect is not dependent from the agonist employed to increase (via cyclic AMP accumulation) contractile force. However, in atria from beta(1)-adrenoceptor antagonist-treated patients, carbachol-induced indirect negative inotropic effect is attenuated.
Wangemann
Thekla
T
Clinic for Cardio-Thoracic Surgery, Martin Luther University of Halle-Wittenberg, D-06097, Halle, Germany.
Giessler
Christine
C
Willmy-Matthes
Pia
P
Silber
Ralf Edgar
RE
Brodde
Otto Erich
OE
D000262:Adenylyl Cyclases / Q000378:metabolism; D018674:Adrenergic Antagonists / Q000494:pharmacology*; D058671:Adrenergic beta-1 Receptor Antagonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000368:Aged; D002217:Carbachol / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006325:Heart Atria / Q000187:drug effects* / Q000201:enzymology; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013726:Terbutaline / Q000494:pharmacology
D018674:Adrenergic Antagonists; D058671:Adrenergic beta-1 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D002316:Cardiotonic Agents; D012701:Serotonin; D006632:Histamine; D002217:Carbachol; D000262:Adenylyl Cyclases; D013726:Terbutaline; D009638:Norepinephrine