α-Adrenoceptors and α -Adrenoceptor-Mediated Positive Inotropic Effects in Failing Human Myocardium

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Abstract
Experiments were designed to characterize cardiac α-adrenoceptors and the a-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 a-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 α-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 β-adrenoceptors was measured. The number of β-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 < 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 β-adrenoceptors and the β-adrenoceptor-mediated positive inotropic effects were reduced in severely failing myocardium. Cardiac α-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 α-adrenoceptors does obviously not occur in the human heart. Because there is no reduction of cardiac α-adrenoceptors but an increased ratio of α-adrenoceptors to the total amount of adrenoceptors, they might serve to contribute to the maintenance of cardiac contractility in severe heart failure, in which β-adrenoceptor-mediated responses are compromised.

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