Different beta-adrenoceptor-effector coupling in human ventricular and atrial myocardium.
To examine whether the downregulation of beta-adrenoceptors is accompanied by reduced beta-adrenoceptor-mediated effects in atrial as well as in ventricular myocardium, we investigated the beta-adrenoceptor-effector coupling in atrial and papillary muscle strips from patients with terminal heart failure (heart transplantation because of dilated cardiomyopathy; New York Heart Association Class IV, NYHA IV) and moderate heart failure (mitral valve replacement, NYHA II-III) and in tissue from non-failing hearts. The isometric force of contraction induced by isoprenaline (0.001-1 mumoll-1) or Ca2+ (1.8-15 mmoll-1) in atrial muscle strips and papillary muscle strips has been measured. We also examined the number of beta-adrenoceptors in both tissues by radioligand binding. The degree of heart failure affected neither the potency (EC50: control: 0.01 (0.001-0.082) mumoll-1; NYHA II-III: 0.01 (0.001-0.125) mumoll-1; NYHA IV: 0.01 (0.001-0.160) mumoll-1) nor the efficacy (NYHA IV: 7.8 +/- 1.0 mN; NYHA II-III: 6.1 +/- 0.7 mN; control: 7.7 +/- 0.9 mN) of the isoprenaline-mediated increase in force of contraction in atrial muscle strips. This is in spite of a reduced number of beta-adrenoceptors in moderately (NYHA II-III) and terminally (NYHA IV) failing atrial myocardium compared to non-failing atrial myocardium (P less than 0.05). In contrast, in papillary muscle strips increasing degrees of heart failure were accompanied by a progressive reduction of the isoprenaline-mediated increase in force of contraction (P less than 0.05) as well as by a progressive decrease of beta-adrenoceptors (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Schwinger
R H
RH
Medizinische Klinik I Universität München Klinikum Grosshadern, Germany.
Böhm
M
M
Pieske
B
B
Erdmann
E
E
D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000378:metabolism; D005260:Female; D006325:Heart Atria / Q000378:metabolism; D006333:Heart Failure / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010210:Papillary Muscles / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol