Platelet alpha 2 adrenoreceptors in chronic congestive heart failure

Abstract

Patients with chronic congestive heart failure (CHF) are known to have elevated plasma concentrations of norepinephrine. Although this elevation of catecholamines in plasma may facilitate myocardial contractility, it may also be toxic to the myocardium in the long term. The alpha 2 adrenoreceptor located on noradrenergic nerve terminals regulates neuronal norepinephrine release by feedback inhibition. This receptor is also located on human blood platelets. This study determines the status of platelet alpha 2 adrenoreceptors in 16 patients with CHF (class I and II in 7 and class III and IV in 9) and in 26 normal volunteers. Specific high-affinity binding of the alpha 2 agonist 3H-clonidine and the alpha 2 antagonist 3H-yohimbine was used to determine the number (B max) of alpha 2 receptors and the dissociation constant (K D) for the 2 ligands. In the control population, the B max (in fmol/mg protein) for 3Hclonidine was 33 ± 2 and for 3H-yohimbine was 165 +- 12. There was a 25% difference in the maximum number of specific binding sites for 3H-clonidine in the class III/IV group (B max 24 ± 2, p < 3.05) and a 43% difference in the maximum number of specific binding sites for 3H-yohimbine (B max 94 ± 9; p < 0.005). There was a smaller but nonsignificant difference in the number of receptors on platelets from patients in the class I and II group. The K D's were similar in all 3 groups. These differences correlated well with the increases in plasma norepinephrine levels between the normal group (273.8 ± 44.1 pg/ml) and the class III/IV group (1333.5 ± 244.9, p < 0.0005). This study supports the hypothesis that increased levels of circulating norepinephrine in CHF lead to a decrease in platelet alpha 2 adrenoreceptors. Further studies should be performed to determine whether pharmacologic stimulation of these receptors might lead to a decrease in the neuronal release of that norepinephrine which might be toxic to the myocardium. Monitoring of platelet alpha 2 adrenoreceptor number may provide a guide to therapy of CHF.