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Time-course changes of nLDL-induced erectile dysfunction

Abstract

Hyperlipidemia is an important risk factor for atherosclerosis and is frequently seen in patients with erectile dysfunction (ED). This study was designed to evaluate whether the acute effect of native low-density lipoprotein (nLDL) on intracavernosal pressure (ICP) is reversible and related to plasma asymmetrical dimethylarginine (ADMA), endogenous inhibition of endothelial nitric oxide synthase (eNOS) levels and eNOS expression in cavernous tissues. Hyperlipidemia was induced by a single dose of intravenous 4 mg kg−1 nLDL. Experiments were performed 72 h (72H), 2 weeks (2W) and 8 weeks (8W) after nLDL injection. Endothelium-dependent relaxations, the ratio of ICP to mean arterial pressure (MAP; ICP/MAP), plasma ADMA levels and eNOS mRNA and protein levels were evaluated. The ICP/MAP ratio decreased in both the 2W and 8W groups. Endothelium-dependent relaxation responses to acetylcholine in the rat thoracic aorta were damaged in the 8W group. Plasma ADMA levels increased in the 8W group. mRNA expression of eNOS decreased in a time-dependent manner, whereas the protein expression increased. These results suggest that acute nLDL injection-induced impairments in erectile functions during an 8-week period are irreversible and might be related to an increase in ADMA levels and changes in the regulation of the eNOS/NO pathway.

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References

  1. 1

    Tikkanen MJ, Jackson G, Tammela T, Assmann G, Palomäki A, Kupari M et al. Erectile dysfunction as a risk factor for coronary heart disease: implications for prevention. Int J Clin Pract 2007; 61: 265–268.

    CAS  Article  Google Scholar 

  2. 2

    Javaroni V, Neves MF . Erectile dysfunction and hypertension: ımpact on cardiovascular risk and treatment. Int J Hypertens 2012; 2012: 11.

    Article  Google Scholar 

  3. 3

    Adams MR, Kinlay S, Blake GJ, Orford JL, Ganz P, Selwyn AP . Atherogenic lipids and endothelial dysfunction: mechanisms in the genesis of ischemic syndromes. Annu Rev Med 2000; 51: 149–167.

    CAS  Article  Google Scholar 

  4. 4

    Wouters K, Shiri-Sverdlov R, van Gorp PJ, van Bilsen M, Hofker MH . Understanding hyperlipidemia and atherosclerosis: lessons from genetically modified ApoE and LDLR mice. Clin Chem Lab Med 2005; 43: 470–479.

    CAS  Article  Google Scholar 

  5. 5

    Kim SC . Hyperlipidemia and erectile dysfunction. Asian J Androl 2000; 2: 161–166.

    CAS  PubMed  Google Scholar 

  6. 6

    Nehra A . Erectile dysfunction and cardiovascular disease: efficacy and safety of phosphodiesterase type 5 inhibitors in men with both conditions. Mayo Clin Proc 2009; 84: 139–148.

    CAS  Article  Google Scholar 

  7. 7

    Hein TW, Liao JC, Kuo L . oxLDL specifically impairs endothelium-dependent, NO-mediated dilation of coronary arterioles. Am J Physiol Heart Circ Physiol 2000; 278: H175–H183.

    CAS  Article  Google Scholar 

  8. 8

    Yi L, Jin X, Chen CY, Fu YJ, Zhang T, Chang H et al. Chemical structures of 4-oxo-flavonoids in relation to inhibition of oxidized low-density lipoprotein (LDL)-induced vascular endothelial dysfunction. Int J Mol Sci 2011; 12: 5471–5489.

    CAS  Article  Google Scholar 

  9. 9

    Li D, Mehta JL . Oxidized LDL, a critical factor in atherogenesis. Cardiovasc Res 2005; 68: 353–354.

    CAS  Article  Google Scholar 

  10. 10

    Ryoo S, Berkowitz DE, Lim HK . Endothelial arginase II and atherosclerosis. Korean J Anesthesiol 2011; 61: 3–11.

    CAS  Article  Google Scholar 

  11. 11

    Harrison DG, Armstrong ML, Freiman PC, Heistad DD . Restoration of endothelium-dependent relaxation by dietary treatment of atherosclerosis. J Clin Invest 1987; 80: 1808–1811.

    CAS  Article  Google Scholar 

  12. 12

    Ihlemann N, Rask-Madsen C, Perner A, Dominguez H, Hermann T, Kober L et al. Tetrahydrobiopterin restores endothelial dysfunction induced by an oral glucose challenge in healthy subjects. Am J Physiol Heart Circ Physiol 2003; 285: H875–H882.

    CAS  Article  Google Scholar 

  13. 13

    Vargas F, Moreno JM, Wangensteen R, Rodriguez-Gomez I, Garcia-Estan J . The endocrine system in chronic nitric oxide deficiency. Eur J Endocrinol 2007; 156: 1–12.

    CAS  Article  Google Scholar 

  14. 14

    Nikoobakht M, Nasseh H, Pourkasmaee M . The relationship between lipid profile and erectile dysfunction. Int J Impot Res 2005; 17: 523–526.

    CAS  Article  Google Scholar 

  15. 15

    Kim JH, Klyachkin ML, Svendsen E, Davies MG, Hagen PO, Carson CC 3rd . Experimental hypercholesterolemia in rabbits induces cavernosal atherosclerosis with endothelial and smooth muscle cell dysfunction. J Urol 1994; 151: 198–205.

    CAS  Article  Google Scholar 

  16. 16

    Jiang JL, Li Ns NS, Li YJ, Deng HW . Probucol preserves endothelial function by reduction of the endogenous nitric oxide synthase inhibitor level. Br J Pharmacol 2002; 135: 1175–1182.

    CAS  Article  Google Scholar 

  17. 17

    Demir O, Murat N, Soner BC, Demir T, Bal E, Can E et al. Acute effects of hypercholesterolemic diet on erectile responses in rats. Urol İnt 2010; 85: 112–117.

    CAS  Article  Google Scholar 

  18. 18

    Billups KL . Erectile dysfunction as a marker for vascular disease. Curr Urol Rep 2005; 6: 439–444.

    Article  Google Scholar 

  19. 19

    Calara F, Dimayuga P, Niemann A, Thyberg J, Diczfalusy U, Witztum JL et al. An animal model to study local oxidation of LDL and its biological effects in the arterial wall. Arterioscler Thromb Vasc Biol 1998; 18: 884–893.

    CAS  Article  Google Scholar 

  20. 20

    Elesber AA, Solomon H, Lennon RJ, Mathew V, Prasad A, Pumper G et al. Coronary endothelial dysfunction is associated with erectile dysfunction and elevated asymmetric dimethylarginine in patients with early atherosclerosis. Eur Heart J 2006; 27: 824–831.

    CAS  Article  Google Scholar 

  21. 21

    Maas R, Schwedhelm E, Albsmeier J, Boger RH . The pathophysiology of erectile dysfunction related to endothelial dysfunction and mediators of vascular function. Vasc Med 2002; 7: 213–225.

    Article  Google Scholar 

  22. 22

    Park K, Lee DG, Kim SW, Paick JS . Dimethylarginine dimethylaminohydrolase in rat penile tissue: reduced enzyme activity is responsible for erectile dysfunction in a rat model of atherosclerosis. Int J İmpot Res 2009; 21: 228–234.

    CAS  Article  Google Scholar 

  23. 23

    Yoshida H, Sasaki K, Namiki Y, Sato N, Tada N . Edaravone, a novel radical scavenger, inhibits oxidative modification of low-density lipoprotein (LDL) and reverses oxidized LDL-mediated reduction in the expression of endothelial nitric oxide synthase. Atherosclerosis 2005; 179: 97–102.

    CAS  Article  Google Scholar 

  24. 24

    Liao JK, Shin WS, Lee WY, Clark SL . Oxidized low-density lipoprotein decreases the expression of endothelial nitric oxide synthase. J Biol Chem 1995; 270: 319–324.

    CAS  Article  Google Scholar 

  25. 25

    Ou Z, Ou J, Ackerman AW, Oldham KT, Pritchard KA Jr . L-4F, an apolipoprotein A-1 mimetic, restores nitric oxide and superoxide anion balance in low-density lipoprotein-treated endothelial cells. Circulation 2003; 107: 1520–1524.

    CAS  Article  Google Scholar 

  26. 26

    Jimenez A, Arriero MM, Lopez-Blaya A, Gonzalez-Fernandez F, Garcia R, Fortes J et al. Regulation of endothelial nitric oxide synthase expression in the vascular wall and in mononuclear cells from hypercholesterolemic rabbits. Circulation 2001; 104: 1822–1830.

    CAS  Article  Google Scholar 

  27. 27

    Murat N, Korhan P, Kizer O, Evcim S, Kefi A, Demir O et al. Resveratrol protects and restores endothelium-dependent relaxation in hypercholesterolemic rabbit corpus cavernosum. J Sex Med 2016; 13: 12–21.

    Article  Google Scholar 

Download references

Acknowledgements

This study was supported by the State Planning Organisation of Turkey (2003K120360).

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Correspondence to N Durmus.

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Durmus, N., Toylu, A., Evcim, S. et al. Time-course changes of nLDL-induced erectile dysfunction. Int J Impot Res 29, 115–119 (2017). https://doi.org/10.1038/ijir.2017.5

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