Cholesterol-induced changes in rabbit arterial smooth muscle sensitivity to adrenergic stimulation.
We evaluated the effects of exposure to high cholesterol levels for 3 h on arterial smooth muscle responses to adrenergic stimulation. Femoral arteries from Dutch belted rabbits were perfused in vitro with a constant-flow variable-pressure perfusion apparentus. After equilibration the vessels were perfused for 180 min more with media supplemented with cholesterol-phospholipid (C/PL) liposomes of molar ratios of 2:1 or 0.5:1. Although resting vascular resistance was unchanged, norepinephrine (NE) concentration-response analyses revealed a fivefold increase in NE sensitivity (P less than 0.001) in the arteries perfused with the cholesterol-enriched liposomes (2:1) compared with control arteries perfused with the 0.5:1 liposome medium. The arteries perfused with the cholesterol-enriched liposomes demonstrated a 60% increase in cholesterol content and a marked (90%) reduction in Na+-K+-ATPase activity. The increased sensitivity of the cholesterol-enriched arteries was not mediated by acute reductions in Na-pump activity, altered endothelial function, adrenergic nerve function, or prostaglandin production. Cholesterol-induced sensitization to NE did demonstrate an absolute dependence on extra-cellular calcium. These findings suggest that an increase in the free cholesterol content of the arterial smooth muscle cell plasma membrane alters membrane permeability to extracellular calcium during adrenergic stimulation.
Broderick
R
R
Department of Physiology and Biochemistry, Medical College of Pennsylvania, Philadelphia 19129.
Bialecki
R
R
Tulenko
T N
TN
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D002784:Cholesterol / Q000008:administration & dosage / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D008081:Liposomes; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D011817:Rabbits; D012964:Sodium / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*
D008081:Liposomes; D002784:Cholesterol; D012964:Sodium; D000109:Acetylcholine; D009638:Norepinephrine