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Involvement of superoxide radical in the impaired endothelium-dependent relaxation of cavernous smooth muscle in hypercholesterolemic rabbits

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Abstract

Involvement of the superoxide radical in impaired relaxation of penile cavernous smooth muscle in hypercholesterolemia was investigated. New Zealand White rabbits (n = 40) were randomly divided into control and treatment groups. The control group (n = 20) received a regular diet while the treatment group (n = 20) was fed a diet of 2% cholesterol for 8 weeks. Blood level of cholesterol in the cholesterol-fed group was significantly higher than that of the control group. The contraction responses of cavernous tissues to norepinephrine were not significantly different in the two groups. The relaxation responses to endothelium-dependent agents (acetylcholine, bradykinin) were significantly reduced in the hypercholesterolemic group compared with the control group. However, the relaxation responses to endothelium-independent agents (papaverine, verapamil) were not significantly different in the two groups. The production of superoxide radicals was significantly higher in the hypercholesterolemic group than in the control group (P < 0.01). The activity of superoxide dismutase (total SOD, Mn-SOD, Cu,ZnSOD) increased significantly in the hypercholesterolemic group compared with the control group (P < 0.05). The activities of catalase and glutathione peroxidase also increased in the hypercholesterolemic group, but were not significantly higher than those of the control group. Therefore, production of the superoxide radicals in rabbit cavernous tissues increases in the state of hypercholesterolemia, which may lead to functional impairment of cavernous smooth muscle relaxation in response to endothelium-mediated stimuli.

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References

  1. Aebi H (1983) Catalase. In: Bermeyer HU, Bermeyer J, Grass M (eds) Methods of enzymatic analysis. Verlag Chemic, Weinheim, p 613

    Google Scholar 

  2. Ahn TY, Saenz de Tejada I (1992) Effects of hypercholesterolemia and nitric oxide synthesis inhibition on rabbit corpus cavernosum tissue. Int J Impotence Res 4 [Suppl 2]:A5

    Google Scholar 

  3. Ahn TY, Azadzoi KM, Saenz de Tejada I (1992) Effects of oxidatively modified low density lipoprotein on corpus cavernosum smooth muscle tone. Int J Impotence Res 4 [Suppl 2]:52

    Google Scholar 

  4. Azadzoi KM, Saenz de Tejada I (1991) Hypercholesterolemia impairs endothelium-dependent relaxation of rabbit corpus cavernosum smooth muscle. J Urol 146:238

    Google Scholar 

  5. Azadzoi KM, Goldstein I (1992) Erectile dysfunction due to atherosclerotic vascular disease: the development of an animal model. J Urol 147:1675

    Google Scholar 

  6. Badwey JA, Karnovsky ML (1979) Production of superoxide dismutase and hydrogen peroxide by an NADH-oxidase in guinea pig polmorphonuclear leukocytes: modulation by nucleotides and divalent cations. J Biol Chem 254:11530

    Google Scholar 

  7. Bossaller C, Habib GB, Yamamoto H, Williams C, Wells S, Henry PD (1987) Impaired muscarinic endothelium-dependent relaxation and cyclic guanosine 5′-monophosphate formation in atherosclerotic human coronary artery and rabbit aorta. J Clin Invest 79:170

    Google Scholar 

  8. Brooks CJ, Steel G, Gilbert JD, Harland WA (1971) Lipids of human atheroma. 4. Characterization of a new group of polar sterol esters from human atherosclerotic plaques. Atherosclerosis 13:223

    Google Scholar 

  9. Casino P, Kilcoyne CM, Cannon III RO, Quyyumi AA, Panza JA (1995) Impaired endothelium-dependent vascular relaxation in patients with hypercholesterolemia extends beyond the muscarinic receptor. Am J Cardiol 75:40

    Google Scholar 

  10. Crapo JD, McCord JM, Fridovich I (1978) Preparation and assay of superoxide dimutase. Methods Enzymol 53:382

    Google Scholar 

  11. Del Boccio G, Lapenna D, Porreca E, Pennelli A, Savini F, Feliciani P, Ricci G, Cuccurullo F (1990) Aortic antioxidant defense mechanisms: time-related changes in cholesterol-fed rabbits. Atherosclerosis 81:127

    Google Scholar 

  12. Dryer SE, Dryer RL, Autor AP (1980) Enhancement of mitochondrial, cyanide-resistant superoxide dismutase in the livers of rat treated with 2,4-dinitrophenol. J Biol Chem 255:1054

    Google Scholar 

  13. Duff GK, McMillan GC, Ritchie AC (1957) The morphology of early atherosclerotic lesions of the aorta demonstrated by the surface technique in rabbits fed cholesterol. Am J Pathol 33:845

    Google Scholar 

  14. Flohe L, Gunzler WA (1984) Assay of glutathione peroxidase. Methods Enzymol 105:114

    Google Scholar 

  15. Fridovich I (1975) Superoxide dismutase. Annu Rev Biochem 44:147

    Google Scholar 

  16. Gryglewski RJ, Palmer RMJ, Moncada S (1986) Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Nature 320:454

    Google Scholar 

  17. Harland WA, Gilbert JD, Steel G, Brooks CJW (1971) Lipids of human atheroma. 5. The occurrence of a new group of polar sterol esters in various stages of human atherosclerosis. Atherosclerosis 13:239

    Google Scholar 

  18. Henriksson P, Bergström K, Edhag O (1985) Experimental atherosclerosis and a possible generation of free radicals. Thrombosis Res 38:195

    Google Scholar 

  19. Jayakody L, Senaratne M, Thomson A, Kappagoda T (1987) Endothelium-dependent relaxation in experimental atherosclerosis in the rabbit. Circ Res 60:251

    Google Scholar 

  20. Jünemann KP, Aufenanger J, Konrad T, Pill J, Berle B, Persson-Junemann C, Alken P (1991) The effect of impaired lipid metabolism on the smooth muscle cell of rabbits. Urol Res 19:271

    Google Scholar 

  21. Kim JH, Klyachkin ML, Svendsen E, Davies MG, Hagen PO, Carson III CC (1994) Experimental hypercholesterolemia in rabbits induces cavernosal atherosclerosis with endothelial and smooth muscle cell dysfunction. J Urol 151:198

    Google Scholar 

  22. Klimov AN, Nagornev VA, Lovyagina TN (1981) Functional characteristics of the endothelium on the dynamics of experimental atherosclerosis. Paroi Arterielle 7:47

    Google Scholar 

  23. Krane RJ, Goldstein I, Saenz de Tejada I (1989) Impotence. N Engl J Med 321:1648

    Google Scholar 

  24. Kugiyama K, Kerns SA, Morrisett JD, Roberts R, Henry PD (1990) Impairment of endothelium-dependent arterial relaxation by lysolecithin in modified low-density lipoproteins. Nature 344:160

    Google Scholar 

  25. McCord JM, Fridovich I (1969) Superoxide dismutase: an enzymatic function for erythrocuprein (hemocuprein). J Biol Chem 244:6049

    Google Scholar 

  26. Ohara Y, Peterson TE, Sayegh HS, Subramanian RR, Wilcox JN, Harrison DG (1995) Dietary correction of hypercholesterolemia in the rabbit normalizes endothelial superoxide anion production. Circulation 92:898

    Google Scholar 

  27. Simon BC, Cunningham LD, Cohen RA (1990) Oxidized low density lipoproteins cause contraction and inhibit endothelium-dependent relaxation in the pig coronary artery. J Clin Invest 86:75

    Google Scholar 

  28. Sreeharan N, Jayakody RL, Senaratne MPJ, Thomson ABR, Kappagoda CT (1986) Endothelium-dependent relaxation and experimental atherosclesis in the rabbit aorta. Can J Physiol Pharmacol 64:1451

    Google Scholar 

  29. Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL (1989) Beyond cholesterol: modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 320:915

    Google Scholar 

  30. Weisiger RA, Fridovich I (1973) Superoxide dismutase: organelle specificity. J Biol Chem 248:3582

    Google Scholar 

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Kim, S.C., Kim, I.K., Seo, K.K. et al. Involvement of superoxide radical in the impaired endothelium-dependent relaxation of cavernous smooth muscle in hypercholesterolemic rabbits. Urol. Res. 25, 341–346 (1997). https://doi.org/10.1007/BF01294663

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  • DOI: https://doi.org/10.1007/BF01294663

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