Skeletal muscle beta-receptors and isoproterenol-stimulated vasodilation in canine heart failure.
To investigate whether heart failure alters beta-adrenergic receptors on skeletal muscle and its associated vasculature, the density of beta-adrenergic receptors, isoproterenol-stimulated adenylate cyclase activity, and coupling of the guanine nucleotide-binding regulatory protein were compared in 18 control dogs and 16 dogs with heart failure induced by 5-8 wk of ventricular pacing at 260 beats/min. Hindlimb vascular responses to isoproterenol were compared in eight controls and eight of the dogs with heart failure. In dogs with heart failure, the density of beta-receptors on skeletal muscle was reduced in both gastrocnemius (control: 50 +/- 5; heart failure: 33 +/- 8 fmol/mg of protein) and semitendinosus muscle (control: 43 +/- 9; heart failure: 27 +/- 9 fmol/mg of protein, both P less than 0.05). Receptor coupling to the ternary complex, as determined by isoproterenol competition curves with and without guanosine 5'-triphosphate (GTP), was unchanged. Isoproterenol-stimulated adenylate cyclase activity was significantly decreased in semitendinosus muscle (control: 52.4 +/- 4.6; heart failure: 36.5 +/- 9.5 pmol.mg-1.min-1; P less than 0.05) and tended to be decreased in gastrocnemius muscle (control: 40.1 +/- 8.5; heart failure: 33.5 +/- 4.5 pmol.mg-1.min-1; P = NS). Isoproterenol-induced hindlimb vasodilation was not significantly different in controls and in dogs with heart failure. These findings suggest that heart failure causes downregulation of skeletal muscle beta-adrenergic receptors, probably due to receptor exposure to elevated catecholamine levels, but does not reduce beta-receptor-mediated vasodilation in muscle.
Frey
M J
MJ
Department of Medicine and Pharmacology, University of Pennsylvania, Philadelphia 19104.
Lanoce
V
V
Molinoff
P B
PB
Wilson
J R
JR
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002303:Cardiac Output, Low / Q000378:metabolism*; D003627:Data Interpretation, Statistical; D004285:Dogs; D006160:Guanosine Triphosphate / Q000378:metabolism; D006439:Hemodynamics; D006614:Hindlimb; D007457:Iodine Radioisotopes; D007545:Isoproterenol / Q000494:pharmacology*; D009132:Muscles / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects*
D007457:Iodine Radioisotopes; D011943:Receptors, Adrenergic, beta; D006160:Guanosine Triphosphate; D000262:Adenylyl Cyclases; D007545:Isoproterenol