Alterations in basal and serotonin-stimulated calcium permeability and vasoconstriction in atherosclerotic aorta.
Hypersensitivity to vasoactive stimuli, a common finding in atherosclerotic arteries, is thought to play an important role in the pathology of arterial and coronary vasospasm and may be a factor in myocardial ischemia and infarction. While this phenomenon is well documented, the underlying mechanism is unknown. The present study used isometric force measurements coupled with 45Ca2+ and Fura 2-AM techniques in aortic smooth muscle to probe transmembrane calcium movements and cytosolic calcium levels in an attempt to determine their relation to altered vasomotion in a rabbit model of dietary atherosclerosis. Following 10 weeks of cholesterol feeding (2%), basal (unstimulated) calcium influx was augmented 1.5-fold in atherosclerotic segments with no change in basal calcium efflux. Serotonin-stimulated calcium uptake was increased 1.9-fold in atherosclerotic segments and was accompanied by a fivefold increase in serotonin vasoconstrictor sensitivity and a 1.4-fold increase in serotonin-stimulated calcium efflux. Endothelial denudation did not alter either force generation or 45Ca2+ movements in serotonin-stimulated segments. In arterial smooth muscle cells dispersed from atherosclerotic vessels, basal and serotonin-stimulated cytosolic calcium levels were augmented approximately 2.3-fold and twofold, respectively. These findings contribute to our understanding of the cellular defects in calcium metabolism, which may ultimately explain the cellular basis of serotonin hypersensitivity in atherosclerotic arteries and certain arterial vasospastic syndromes in this disease state.
Stepp
D W
DW
Department of Physiology, Medical College of Pennsylvania, Philadelphia 19129.
Tulenko
T N
TN
D000818:Animals; D001011:Aorta / Q000503:physiopathology*; D001161:Arteriosclerosis / Q000503:physiopathology*; D002118:Calcium / Q000493:pharmacokinetics*; D003600:Cytosol / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D010539:Permeability; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology*; D014661:Vasoconstriction
D008055:Lipids; D012701:Serotonin; D002118:Calcium