Intracellular distribution of adrenoceptors in the failing human myocardium.
Although it is increasingly recognized that the density of cardiac membrane-bound beta adrenoceptors declines in heart failure, the mechanisms involved are unclear. Furthermore, it is not known whether cardiac alpha-1 adrenoceptors are similarly affected. Inasmuch as agonist-induced desensitization results in translocation of adrenoceptors from the plasma membrane to an intracellular vesicular fraction, we determined the intracellular distribution of cardiac adrenoceptors in two groups: group 1 (n = 9) consisted of papillary muscles from patients with mild-to-moderate heart failure undergoing valve replacement, and group 2 (n = 8) consisted of severely failing hearts removed during orthotopic cardiac transplantation. The density of cardiac beta adrenoceptors was lower in membranes from group 2 (17.8 +/- 3.3 fmol/mg protein vs 27.8 +/- 3.7 fmol/mg in group 1; (p less than 0.01), and the percentage of beta receptors recovered in the vesicular fraction was higher in group 2 (47.1 +/- 3.3% vs 36.8 +/- 5.0% in group 1; p less than 0.01). In group 1 but not group 2 there was a significant inverse correlation (r = -0.87; p less than 0.001) between the density of membrane-bound beta receptors and the percentage of beta receptors recovered in the vesicular fraction. Alpha-1 adrenoceptors were lower in both membrane and vesicular fraction of group 2 compared to group 1; in group 2 but not group 1 there was a significant negative correlation between the density of membrane-bound alpha-1 adrenoceptors and the percentage of alpha-1 receptors in the vesicular fraction (r = -0.8; p less than 0.01). These results suggest that the regulation of alpha-1 and beta adrenoceptors differs in the failing myocardium. Furthermore, agonist-induced desensitization may play a predominant role only in mild-to-moderate heart failure.
Limas
C J
CJ
Department of Medicine, University of Minnesota School of Medicine, Minneapolis 55455.
Limas
C
C
Goldenberg
I F
IF
D002302:Cardiac Output; D002462:Cell Membrane / Q000032:analysis; D005260:Female; D006331:Heart Diseases / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D006346:Heart Septum / Q000032:analysis; D006352:Heart Ventricles / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000032:analysis*; D009638:Norepinephrine / Q000097:blood; D010210:Papillary Muscles / Q000032:analysis; D011669:Pulmonary Wedge Pressure; D011941:Receptors, Adrenergic / Q000032:analysis*; D013318:Stroke Volume
D011941:Receptors, Adrenergic; D009638:Norepinephrine