Beta-adrenergic receptor distribution among muscle fiber types and resistance arterioles of white, red, and intermediate skeletal muscle.
The pathophysiological effects of congestive heart failure and physiological effects of exercise training on skeletal muscle may be mediated in part by modulation of beta-adrenergic receptor density. To shed light on the physiological role of skeletal muscle beta-receptors, their density and distribution were characterized in muscle fibers and resistance arterioles of whole tissue slices of three rat hindquarter muscles differing markedly in fiber type composition and capacities for oxidative metabolism and vasodilatation. Binding isotherms and quantitative light microscopic autoradiographic localization of receptors were performed by incubating tissue slices in selected concentrations of [125I]cyanopindolol with and without 10(-5) M l-propranolol. Muscle fiber types were delineated in adjacent sections by histochemical staining of myofibrillar ATPase activity at pH 4.5-4.55. The total tissue content of receptors (Bmax) was nearly threefold greater in the soleus, a muscle consisting almost entirely of slow-twitch (type I) fibers than in superficial white vastus lateralis, a muscle composed of greater than 95% fast-twitch (type IIb) fibers. Bmax was intermediate in gastrocnemius, a mixed fiber muscle (all differences p less than 0.01). Receptor affinity for radioligand was higher in the white vastus than in the mixed fiber and slow-twitch muscles (Kd = 3.5 +/- 0.4 pM for white vastus versus 6.8 +/- 0.8 and 6.4 +/- 1.1 pM in gastrocnemius and soleus, respectively; both p less than 0.01 versus white vastus). Disparities in Bmax among muscles were due entirely to differences in receptor densities of skeletal muscle cells as shown autoradiographically. Furthermore, variations in Bmax of the three skeletal muscles were directly related to percentage of type I fibers (r = 0.99; p less than 0.001), which had a beta-receptor density that was approximately 4.5-fold greater than in superficially located type IIb fibers, 3.2-fold greater than in intermediate depth type IIb fibers, and 2.0-fold greater than in type IIa fibers. In contrast, grain densities of resistance arterioles were similar regardless of surrounding skeletal muscle fiber type composition. However, resistance arterioles were 2.5- and 6.1-fold more numerous in the slow-twitch soleus than in the gastrocnemius and superficial white vastus, respectively (all differences p less than 0.01). We conclude that beta-receptor density of rat hindquarter skeletal muscles is directly proportional to percentage of slow-twitch fibers, while receptor affinity for antagonist is higher in fast-twitch than in slow-twitch or mixed fiber muscles.(ABSTRACT TRUNCATED AT 250 WORDS)
Martin
W H
WH
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Murphree
S S
SS
Saffitz
J E
JE
D000251:Adenosine Triphosphatases / Q000032:analysis; D000818:Animals; D001158:Arteries / Q000294:innervation*; D001160:Arterioles / Q000294:innervation*; D001345:Autoradiography; D005629:Frozen Sections; D006651:Histocytochemistry; D009132:Muscles / Q000098:blood supply / Q000294:innervation* / Q000378:metabolism; D009210:Myofibrils / Q000201:enzymology; D009246:NADH Tetrazolium Reductase / Q000032:analysis; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000032:analysis*
D011943:Receptors, Adrenergic, beta; D009246:NADH Tetrazolium Reductase; D000251:Adenosine Triphosphatases