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Effects of a high-cholesterol diet on arterial wall thickness and vascular reactivity in young rabbits

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Summary

Cholesterol enrichment of arteries may induce biochemical and structural abnormalities in vascular smooth muscle resulting in increased arterial contractile sensitivity. We studied the effects of a high-cholesterol diet on arterial structural properties and vascular reactivity in young rabbits. In vivo measurements of aortic intimal-plus-medial thickness using high resolution ultrasound imaging were obtained before and after 3 weeks of a high-cholesterol diet in 12 rabbits (group 2) and compared to data from 12 animals a cholesterol-free diet fed (group 1). Six rabbits (group 3) were studied before and after a 3-week, high-cholesterol diet and after a subsequent 13-week, cholesterol-free recovery diet. Blood pressure responsiveness to noradrenaline was evaluated before and at the end of each diet period. In groups 2 and 3, high dietary cholesterol caused an increase in intimal-plus-medial thickness from 0.31 mm and 0.33 mm to 0.88 mm and 0.89 mm, respectively (p<0.001). Plasma cholesterol concentration rose from 0.9 ±0.26 mmol/l to 36.7 ± 8.56 mmol/l. There was no change in group 1. In group 3, intimal-plus-medial thickness remained increased (1.01 mm) following the cholesterol-free recovery diet despite normal plasma cholesterol. Blood pressure responsiveness to noradrenaline was markedly increased after the high-cholesterol diet (p<0.001) in groups 2 and 3 and after the cholesterol-free recovery diet in group 3 (p<0.001), and was directly related to intimal-plus-medial thickness (r=0.84;p<0.001). The data indicate that short-term high dietary cholesterol in the early life of rabbits causes long-lasting biochemical and structural arterial wall abnormalities, which might not only explain the observed increase in blood pressure responsiveness to noradrenaline, but could also lead to persistent functional vascular smooth muscle alterations. The result may be a predisposition to increased vascular smooth muscle response to high dietary cholesterol in adult life and development of high blood pressure and atherosclerosis.

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Abbreviations

P art :

mean arterial pressure

ACAT:

acyl-CoA-cholesterol-acyl-transferase

EDRF:

endothelium-derived relaxing factor

EDCF:

endothelium-derived contracting factor

NA:

noradrenaline

References

  1. Altiere RJ, Kriritsy-Roy JA, Catravas JD (1986) Acetylcholine-induced contractions in isolated rabbit pulmonary arteries. Role of thromboxane A2. J Pharmacol Exp Ther 236:535–541

    Google Scholar 

  2. Anitschkow N, Chalatow S (1913) Über experimentelle Cholesterinsteatose und ihre Bedeutung für die Entstehung einiger pathologischer Prozesse. Zentralbl Allg Pathol 24:1–9

    Google Scholar 

  3. Bialecki RA, Tulenko TN (1989) Excess membrane cholesterol alters calcium channels in arterial smooth muscle. Am J Physiol 257:306–314

    Google Scholar 

  4. Blumelein SL, Sievers R, Kidd P, Parmley WW (1984) Mechanism of protection from atherosclerosis by verapamil in the cholesterol-fed rabbit. Am J Cardiol 54:884–889

    Google Scholar 

  5. Bossaller C, Fleck E (1989) Endothelium-derived relaxing factor in human coronary artery. Z Kardiol 78 [Suppl 6]:59–63

    Google Scholar 

  6. Förstermann U, Warmut G, Dudel C, Alheid U (1989) Formation and functional importance of endothelium-derived relaxing factor (EDRF) and prostaglandins in the microcirculation. Z Kardiol 78 [Suppl 6]:85–91

    Google Scholar 

  7. Furchgott RF, Zawadski JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:373–376

    Google Scholar 

  8. Ginsburg R, Davis K, Bristow MR, McKennett K, Kodsi SR, Billingham EM, Schroeder JS (1983) Calcium antagonists suppress atherogenesis in aorta but not in the intramural coronary arteries of cholesterol-fed rabbits. Lab Invest 49:154–158

    Google Scholar 

  9. Gryglewski RJ, Bunting S, Moncada S, Flower RJ, Vane JR (1976) Arterial walls are protected against deposition of platelet thrombi by a substance which they make from prostaglandin endoperoxides. Prostaglandins 12:685–713

    Google Scholar 

  10. Habib JB, Bossaller C, Wells S, Williams C, Morrisett JD, Henry PD (1986) Preservation of endothelium-dependent vascular relaxation in cholesterol fed rabbit by treatment with the calcium blocker PN 200110. Circ Res 58:305–309

    Google Scholar 

  11. Hennerici M, Reifschneider G, Trockel U, Aulich A (1984) Detection of early atherosclerotic lesions by duplex scanning of the carotid artery. J Clin Ultrasound 12:455–464

    Google Scholar 

  12. Henry PD (1985) Atherosclerosis, calcium and calcium antagonists. Circulation 72:456–459

    Google Scholar 

  13. Hopkins NK, Gorman RR (1981) Regulation of endothelium cell cyclic nucleotide metabolism by prostacyclin. J Clin Invest 67:540–546

    Google Scholar 

  14. Jayakody L, Senaratne M, Thomson ABR, Kappagoda T (1986) Endothelium-dependent relaxation in experimental atherosclerosis in the rabbit. Circ Res 60:251

    Google Scholar 

  15. Kifor I, Dzau VJ (1987) Endothelial renin-angiotensin pathway: evidence for intracellular synthesis and secretion of angiotensin. Circ Res 60:422–428

    Google Scholar 

  16. Koga T, Takata Y, Kobayashi K, Takishita S, Yamashita Y, Fujishima M (1989) Age and hypertension promote endothelium-dependent contractions to acetylcholin in the aorta of the rat. Hypertension 14:542–548

    Google Scholar 

  17. Locher R, Neyses L, Stimpel M, Kuffer B, Vetter W (1984) The cholesterol content of the human erythrocyte influences calcium influx through the channel. Biochem Biophys Res Commun 124:822–828

    Google Scholar 

  18. Ludmer PL, Selwyn AP, Shook TL, Wayne RR, Mudge GH, Alexander RW, Ganz P (1986) Paradoxical vasoconstriction produced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med 315:1046–1051

    Google Scholar 

  19. Ludwig M, Kraft K, Rücker W, Hüther AM (1989) Die Diagnose sehr früher arteriosklerotischer Gefäßwandverän-derungen mit Hilfe der Duplexsonographie. Klin Wochenschr 67:442–446

    Google Scholar 

  20. Ludwig M, Wetzig H, Sauer A, Vetter H (1990) Erfahrungen mit der Anwendung eines intravasalen 6 French Endosonographiekatheters in vivo. Klin Wochenschr 68:570–575

    Google Scholar 

  21. Ludwig M, Stumpe KO, Sauer A, Kolloch R, Goertz U, Vetter H (1991) Short-term high dietary cholesterol in early life induces persistent increases in arterial wall thickness and vascular reactivity to noradrenaline. J Hypertens (in press)

  22. Lüscher TF, Vanhoutte PM (1986) Endothelium-dependent contractions to acetylcholine in the aorta of spontaneously hypertensive rats. Hypertension 8:344–348

    Google Scholar 

  23. Meyer WW (1968) Die Arteriosklerose im Tierexperiment. In: Staemmler M (Hrsg) Lehrbuch der speziellen pathologischen Anatomie. Erg. Bd. I, 1. Hälfte, 3. Lfrg. W. de Gruyter & Co, Berlin, S 591–652

  24. Moncada S, Herman AG, Higgs EA, Vane JR (1977) Differential formation of prostacyclin (PGX or PGI2) by layers of the arterial wall — an explanation for the anti-thrombotic properties of vascular endothelium. Thromb Res 11:323–344

    Google Scholar 

  25. Nees S (1987) Neuere Erkenntnisse zur Physiologie und Pathophysiologie des Gefäßendothels, vor allem im Rahmen der Atherogenese. Internist 28:699–710

    Google Scholar 

  26. Pignoli P, Tremoli E, Poli A, Oreste PL, Paoletti R (1986) Intimal plus medial thickness of arterial wall: a direct measurement with ultrasound imaging. Circulation 74:1399–1406

    Google Scholar 

  27. Ragazzi E, Froldi G, Chinellato A, De Biasi M, Pandolfo L, Prosdocimi M, Caparrotta L, Fassina G (1988) Endothelium-mediated relaxation of aortas from hypercholesterolemic rabbits: effect of acetylcholine and ATP. Pharmacol Res Commun 20 [Suppl 2]:321

    Google Scholar 

  28. Ross R (1986) The pathogenesis of atherosclerosis — an update. N Engl J Med 314:488–500

    Google Scholar 

  29. Rüthlein VM, Spengel FA (1988) Diagnostik symptomatischer Plaques in den Carotiden bei Patienten mit neurologischen ischämischen Ereignissen. VASA 23:202–205

    Google Scholar 

  30. Sachinidis A, Mengden T, Locher R, Brunner C, Vetter W (1990) Novel cellular activities for low density lipoprotein in vascular smooth muscle cells. Hypertension 15(6): Part 2

  31. Schuster HM, Kröner KK, Keller C, Spengel FA, Wolfram G, Zöllner N (1987) Atherosclerosis of the carotid arteries documented by duplex scan as a predictor of coronary artery disease in familial hyperlipidemias. Klin Wochenschr 65:34–39

    Google Scholar 

  32. Sreeharan N, Jayakody RL, Senaratne M, Thomson ABR, Kappagoda T (1986) Endothelium-dependent relaxation and experimental atherosclerosis in the rabbit aorta. Can J Physiol Pharmacol 64:1451

    Google Scholar 

  33. Subbiah MTR, Sprinkle JD, Rymaszewski Z, Yunker RL (1989) Short-term exposure to high dietary cholesterol in early life: arterial changes and response after normalization of plasma cholesterol. Am J Clin Nutr 50:68–72

    Google Scholar 

  34. Tesfamariam B, Weisbrod RM, Cohen RA (1989) Augmented adrenergic contractions of carotid arteries from cholesterol-fed rabbits due to endothelial cell dysfunction. J Cardiovasc Pharmacol 13(6):820–825

    Google Scholar 

  35. Usui H, Kurahashi K, Shirahase H, Fukui K, Fujiwara M (1987) Endothelium-dependent vasoconstriction in response to noradrenaline in the canine cerebral artery. Jpn J Pharmacol 44:228–231

    Google Scholar 

  36. Vallance P, Collier J, Moncada S (1989) Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man. Lancet 28:997–1000

    Google Scholar 

  37. Vane JR, Gryglewski RJ, Botting RM (1987) The endothelial cell as a metabolic and endocrine organ. Trends Pharmacol Sci 8:491

    Google Scholar 

  38. Vanhoutte PM, Lüscher TF (1989) Endothelium-dependent vasoconstriction. In: Rubanyi GM, Vanhoutte PM (eds) Endothelium-derived contracting factors. Karger, Basel, pp 1–7

    Google Scholar 

  39. Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T (1988) A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332:411–415

    Google Scholar 

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Authors and Affiliations

  1. Medizinische Universitäts-Poliklinik, Wilhelmstrasse 35–37, W-5300, Bonn 1, Germany

    M. Ludwig, K. O. Stumpe, A. Sauer, R. Kolloch, U. Goertz & H. Vetter

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  1. M. Ludwig
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  2. K. O. Stumpe
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  3. A. Sauer
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  4. R. Kolloch
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  5. U. Goertz
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  6. H. Vetter
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Ludwig, M., Stumpe, K.O., Sauer, A. et al. Effects of a high-cholesterol diet on arterial wall thickness and vascular reactivity in young rabbits. Clin Investig 70, 105–112 (1992). https://doi.org/10.1007/BF00227349

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  • DOI: https://doi.org/10.1007/BF00227349

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