AJP - Heart and Circulatory Physiology, Vol 257, Issue 1 170-H178, Copyright © 1989 by American Physiological Society

ARTICLES

Cholesterol-induced changes in rabbit arterial smooth muscle sensitivity to adrenergic stimulation

R. Broderick, R. Bialecki and T. N. Tulenko
Department of Physiology and Biochemistry, Medical College of Pennsylvania, Philadelphia 19129.

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.

This article has been cited by other articles:

				J. S. Bystriansky and J. S. Ballantyne Gill Na+-K+-ATPase activity correlates with basolateral membrane lipid composition in seawater- but not freshwater-acclimated Arctic char (Salvelinus alpinus) Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2007; 292(2): R1043 - R1051. [Abstract] [Full Text] [PDF]

				C. M. C. Dupasquier, A.-M. Weber, B. P. Ander, P. P. Rampersad, S. Steigerwald, J. T. Wigle, R. W. Mitchell, E. A. Kroeger, J. S. C. Gilchrist, M. M. Moghadasian, et al. Effects of dietary flaxseed on vascular contractile function and atherosclerosis during prolonged hypercholesterolemia in rabbits Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2987 - H2996. [Abstract] [Full Text] [PDF]

				Q-W Xu, R B Scott, D T M Tan, and E A Shaffer Altered migrating myoelectrical complex in an animal model of cholesterol gallstone disease: the effect of erythromycin Gut, December 1, 1998; 43(6): 817 - 822. [Abstract] [Full Text] [PDF]

				T. N. Tulenko, M. Chen, P. E. Mason, and R. P. Mason Physical effects of cholesterol on arterial smooth muscle membranes: evidence of immiscible cholesterol domains and alterations in bilayer width during atherogenesis J. Lipid Res., May 1, 1998; 39(5): 947 - 956. [Abstract] [Full Text]

				G. Nickenig, A. Sachinidis, F. Michaelsen, M. Bohm, S. Seewald, and H. Vetter Upregulation of Vascular Angiotensin II Receptor Gene Expression by Low-Density Lipoprotein in Vascular Smooth Muscle Cells Circulation, January 21, 1997; 95(2): 473 - 478. [Abstract] [Full Text]

				D. W. Stepp and J. C. Frisbee Augmented adrenergic vasoconstriction in hypertensive diabetic obese Zucker rats Am J Physiol Heart Circ Physiol, March 1, 2002; 282(3): H816 - H820. [Abstract] [Full Text] [PDF]