Summary
Coronary arteries and aortic rings were isolated from rabbits fed either a control diet or a high cholesterol (1 to 2%) diet for 8 to 11 weeks and studied for their vasoactive properties to a variety of vasoconstrictor and vasodilator agents. Perfused coronary arteries without intact endothelium constrict markedly to a thromboxane A2 agonist (i.e., carbocyclic thromboxane A2, CTA2) and dilate markedly to iloprost, a prostacyclin analog. No differences occurred between the coronary arteries isolated from control or atherosclerotic rabbits. Additional studies were conducted on rabbit aortic vascular smooth muscle rings containing functionally intact endothelium and in rings denuded of their endothelium. Acetylcholine (20 to 2000 ng/ml) neither constricted nor dilated control aortic rings without endothelium, and markedly dilated aortic rings with intact endothelium in a concentration dependent manner. In atherosclerotic aortic rings, acetylcholine constricted preparations without endothelium, and dilated rings with endothelium to a much lesser extent than that observed in control rings. Similar reductions in responsiveness occurred with adenosine diphosphate (ADP), another endothelium-dependent vasodilator, but not with iloprost, a nonendothelium-dependent dilator. No differences were observed in constrictor responses to norepinephrine. Aortae from atherosclerotic rabbits produced less prostacyclin in response to arachidonic acid than control aortae. These data point to an important role of the endothelium in modulating the vascular response to vasodilators in atherosclerotic rabbit arterial vessels.
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References
Tulenko T, Broderick R. The role of cholesterol in arterial wall function and its alteration in vascular disease. In:Re cent advances in arterial diseases: atherosclerosis, hypertension, and vasospasm. Alan R. Liss, Inc., 1986. Pp. 75–101.
Hoff HF, Heideman CL, Gotto AM, et al. Apolipoprotein B retention in the grossly normal and atherosclerotic human aorta.Circ Res 1977;41:684–690.
Schroeder JS, Bolen JL, Quint RA, et al. Provocation of coronary spasm with ergonovine maleate.Am J Cardiol 1977;40:487–491.
Osborne JA, Lefer AM. Increased severity of acute myocardial ischemia in experimental atherosclerosis.Fred Proc 1987;46:415.
Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine.Nature 1980;288:373–376.
De Mey JG, Vanhoutte PM. Role of the intima in cholinergic and purinergic relaxation of isolated canine femoral arteries.J Physiol (Land) 1981;316:347–355.
Ogletree MJ, Smith JB, Lefer AM. Actions of prostaglandins on isolated perfused cat coronary arteries.Am J Physiol 1978;235:H400-H406.
Smith EF III, Lefer AM, Nicolaou KC. Mechanism of coronary vasoconstriction induced by carbocyclic thromboxane A2.Am J Physiol 1981;240:H493-H497.
Darius H. Platelet and vascular effects of iloprost (ZK 36.374) and its stereoisomer ZK 36.375 — two chemically stable prostacyclin analogues. In: Schror K, ed.Prostaglandins and other eicosaniods in the cardiovascular system. Proc. 2nd Int. Symp., Nurnberg-Furth 1984. Basel:Karger, 1985. pp. 454–464.
Ingerman-Wojenski C, Silver MJ, Smith JB, Macarak E. Bovine endothelial cells in culture produce thromboxane as well as prostacyclin.J Clin Invest 1981;67:1292–1296.
Constantinides P, Booth J, Carlson G. Production of advanced cholesterol atherosclerosis in the rabbit.Arch Pathol 1960;70:712–724.
Senges J, Weihe E, Brachmann J, et al. Effects of hyper-cholesterolaemia without ischemia on some electrophysiological and ultrasturctural properties of the rabbit heart.J Molec Cell Cardiol 1981;13:253–264.
Sinzinger H. Role of platelets in atherosclerosis.Sem Thromb Hemostas 1986;12:124–133.
Heistad DD, Armstrong ML, Marcus ML, et al. Augmented responses to vasoconstrictor stimuli in hypercholesterolemic and atherosclerotic monkeys.Circ Res 1984;54:711–718.
Gryglewski RJ, Deminska-Kiec A, Zmuda A, et al. Prostacyclin and thromboxane A2 biosynthesis capacities of heart, arteries, and platelets at various stages of experimental atherosclerosis in rabbits.Atherosclerosis 1978;31:385–394.
Sinzinger H, Clopath P, Silberbauer K. The effect of ballooning on minipig aortic prostacyclin formation—a time course.Artery 1980;8:23–29.
Boeynaems JM, Galand N, Ketelbant P. Prostacyclin production by the deendothelialized rabbit aorta.J Clin Invest 1985;76:7–14.
Henry PD, Yokoyama M. Supersensitivity of atherosclerotic rabbit aorta to ergonovine. Mediation by a serotonergic mechanism.J Clin Invest 1980;66:306–313.
Freiman PC, Mitchell GC, Heistad, et al. Atherosclerosis impairs endothelium-dependent vascular relaxation to acetylcholine and thrombin in primates.Circ Res 1986;58:783–789.
Verbeuren TJ, Jordaens FH, Zonnekeyn LL, et al. Effect of hypercholesterolemia on vascular reactivity in the rabbit. I. Endothelium-dependent and endothelium-independent contractions and relaxations in isolated arteries of control and hypercholesterolemic rabbits.Circ Res 1986;58:552–564.
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This study was supported in part by Research Grant No. HL-25575 from the National Heart Lung and Blood Institute of the NIH.
John A. Osborne is a Predoctoral Fellow of the Foerderer Foundation. Jian-zhong Sun is a WHO Postdoctoral Fellow.
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Lefer, A.M., Osborne, J.A., Yanagisawa, A. et al. Influence of atherosclerosis on vascular responsiveness in isolated rabbit vascular smooth muscle. Cardiovasc Drug Ther 1, 385–391 (1987). https://doi.org/10.1007/BF02209080
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DOI: https://doi.org/10.1007/BF02209080