Alpha-adrenoceptors and alpha-adrenoceptor-mediated positive inotropic effects in failing human myocardium.
Experiments were designed to characterize cardiac alpha-adrenoceptors and the alpha-adrenoceptor-mediated positive inotropic effects in human myocardial tissue from patients with moderate New York Heart Association (NYHA) class II-III and severe (NYHA class IV) heart failure. The number of cardiac alpha-adrenoceptors was low but similar in moderate and severe heart failure (NYHA class II-III: 6.7 +/- 0.8 fmol/mg protein 3H-prazosin bound, n = 12; NYHA class IV: 7.4 +/- 0.9 fmol/mg protein 3H-prazosin bound, n = 9; NS). Correspondingly, the alpha-adrenoceptor-mediated positive inotropic effect (phenylephrine in the presence of propranolol) did not significantly differ in both groups. In the same hearts, the number of beta-adrenoceptors was measured. The number of beta-adrenoceptors was significantly reduced in severe heart failure (NYHA class II-III: 22.0 +/- 1.5 fmol/mg protein 3H-CGP 12177 bound, n = 12; NYHA class IV: 11.9 +/- 0.8 fmol/mg protein 3H-CGP 12177 bound, n = 9; p less than 0.05). The positive inotropic effect of isoprenaline was significantly reduced in NYHA class IV. The positive inotropic effect of Ca2+ was similar in both groups. In conclusion, cardiac beta-adrenoceptors and the beta-adrenoceptor-mediated positive inotropic effects were reduced in severely failing myocardium. Cardiac alpha-adrenoceptors and the positive inotropic effect resulting from their stimulation is unchanged. Therefore, down regulation in response to increased sympathetic stimulation or a compensatory increase of alpha-adrenoceptors does obviously not occur in the human heart.(ABSTRACT TRUNCATED AT 250 WORDS)
Böhm
M
M
Medizinische Klinik I der Universität München, Klinikum Grosshadern, Munich, F.R.G.
Diet
F
F
Feiler
G
G
Kemkes
B
B
Erdmann
E
E
D000328:Adult; D000368:Aged; D002118:Calcium / Q000494:pharmacology; D005260:Female; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000503:physiopathology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D007545:Isoproterenol; D002118:Calcium