Exercise prevents western diet-associated erectile dysfunction and coronary artery endothelial dysfunction: Response to acute apocynin and sepiapterin treatment

American Journal of Physiology - Regulatory Integrative and Comparative Physiology

Volumn 305, Issue 4, 2013, Pages

  La Favor, Justin D ^a   Anderson, Ethan J ^a,b   Dawkins, Jillian T ^a,b   Hickner, Robert C ^a,b   Wingard, Christopher J ^a,b  

^a EAST CAROLINA UNIVERSITY   (United States)

^b EAST CAROLINA UNIVERSITY   (United States)

Author keywords

Diet induced obesity; Endothelial nitric oxide synthase uncoupling; High fat high sucrose; High intensity interval training; NADPH oxidase

Indexed keywords

APOCYNIN; CHOLESTEROL; FATTY ACID; GLUCOSE; SEPIAPTERIN; 5,6,7,8-TETRAHYDROBIOPTERIN; ACETOPHENONE DERIVATIVE; BIOPTERIN; DRUG DERIVATIVE; ENZYME INHIBITOR; PTERIN DERIVATIVE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; TETRAHYDROBIOPTERIN; VASODILATOR AGENT;

AEROBIC EXERCISE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BODY WEIGHT; CARBOHYDRATE DIET; CHOLESTEROL BLOOD LEVEL; CONCENTRATION RESPONSE; CONTROLLED STUDY; CORONARY ARTERY CONSTRICTION; CORONARY ARTERY DILATATION; CORONARY ARTERY DISEASE; CORONARY ARTERY ENDOTHELIAL DYSFUNCTION; CORPUS CAVERNOSUM; ELECTROSTIMULATION; ENDOTHELIAL DYSFUNCTION; ERECTILE DYSFUNCTION; EX VIVO STUDY; FAT MASS; GLUCOSE BLOOD LEVEL; IMMOBILIZATION; LEFT ANTERIOR DESCENDING CORONARY ARTERY; LIPID DIET; MALE; MEAN ARTERIAL PRESSURE; MYOGRAPHY; NONHUMAN; OBESITY; OXIDATIVE STRESS; PRIORITY JOURNAL; RAT; TREADMILL EXERCISE; VASCULAR TISSUE; OUTCOME ASSESSMENT; PENIS ERECTION; VASCULAR ENDOTHELIUM; ANIMAL; COMPARATIVE STUDY; CORONARY BLOOD VESSEL; DIET-INDUCED OBESITY; DISEASE MODEL; DOSE RESPONSE; DRUG EFFECT; ENDOTHELIAL NITRIC OXIDE SYNTHASE UNCOUPLING; HIGH-FAT HIGH-SUCROSE; HIGH-INTENSITY INTERVAL TRAINING; KINESIOTHERAPY; METABOLISM; METHODOLOGY; PATHOPHYSIOLOGY; SEDENTARY LIFESTYLE; SPRAGUE DAWLEY RAT; TIME; VASODILATATION;

DIET-INDUCED OBESITY; ENDOTHELIAL NITRIC OXIDE SYNTHASE UNCOUPLING; HIGH-FAT HIGH-SUCROSE; HIGH-INTENSITY INTERVAL TRAINING; NADPH OXIDASE;

ACETOPHENONES; ANIMALS; BIOPTERIN; CORONARY ARTERY DISEASE; CORONARY VESSELS; DIET, HIGH-FAT; DISEASE MODELS, ANIMAL; DOSE-RESPONSE RELATIONSHIP, DRUG; ELECTRIC STIMULATION; ENDOTHELIUM, VASCULAR; ENZYME INHIBITORS; ERECTILE DYSFUNCTION; EXERCISE THERAPY; MALE; NADPH OXIDASE; OBESITY; OXIDATIVE STRESS; PENILE ERECTION; PTERINS; RATS; RATS, SPRAGUE-DAWLEY; SEDENTARY LIFESTYLE; TIME FACTORS; VASODILATION; VASODILATOR AGENTS;

EID: 84881650063     PISSN: 03636119     EISSN: 15221490     Source Type: Journal    
DOI: 10.1152/ajpregu.00049.2013     Document Type: Article

References (67)

1. Adams V, Linke A, Krankel N, Erbs S, Gielen S, Möbius-Winkler S, Gummert JF, Mohr FW, Schuler G, Hambrecht R. Impact of regular physical activity on the NAD(P)H oxidase and angiotensin receptor system in patients with coronary artery disease. Circulation 111: 555-562, 2005.
2. Alp NJ, Channon KM. Regulation of endothelial nitric oxide synthase by tetrahydrobiopterin in vascular disease. Arterioscler Thromb Vasc Biol 24: 413-420, 2004.
3. Anderson EJ, Yamazaki H, Neufer PD. Induction of endogenous uncoupling protein 3 suppresses mitochondrial oxidant emission during fatty acid-supported respiration. J Biol Chem 282: 31257-31266, 2007.
4. Angulo J, Peiró C, Cuevas P, Gabancho S, Fernández A, González-Corrochano R, La Fuente JM, Baron AD, Chen KS, Saenz de Tejada I. The novel antioxidant, AC3056 (2,6-di-t-butyl-4-([dimethyl-4-methoxy-phenylsilyl] methyloxy) phenol), reverses erectile dysfunction in diabetic rats and improves NO-mediated responses in penile tissue from diabetic men. J Sex Med 6: 373-387, 2009.
5. Ayta IA, McKinlay JB, Krane RJ. The likely worldwide increase in erectile dysfunction between 1995 and 2025 and some possible policy consequences. BJU Int 84: 50-56, 1999.
6. Bergholm R, Mäkimattila S, Valkonen M, Liu ML, Lahdenperä S, Taskinen MR, Sovijärvi A, Malmberg P, Yki-Järvinen H. Intense physical training decreases circulating antioxidants and endothelium-dependent vasodilation in vivo. Atherosclerosis 145: 341-349, 1999.
7. Bivalacqua TJ, Usta MF, Kendirci M, Pradhan L, Alvarez X, Champion HC, Kadowitz PJ, Hellstrom WJG. Superoxide anion production in the rat penis impairs erectile function in diabetes: influence of in vivo extracellular superoxide dismutase gene therapy. J Sex Med 2: 187-198, 2005.
8. Borgquist R, Gudmundsson P, Winter R, Nilsson P, Willenheimer R. Erectile dysfunction in healthy subjects predicts reduced coronary flow velocity reserve. Int J Cardiol 112: 166-170, 2006.
9. Cai H, Harrison DG. Endothelial dysfunction in cardiovascular disease: the role of oxidant stress. Circ Res 87: 840-844, 2000.
10. Castor LR, Locatelli KA, Ximenes VF. Pro-oxidant activity of apocynin radical. Free Radic Biol Med 48: 1636-1643, 2010.
11. Channon KM. Tetrahydrobiopterin: regulator of endothelial nitric oxide synthase in vascular disease. Trends Cardiovasc Med 14: 323-327, 2004.
12. de Moraes C, Davel AP, Rossoni LV, Antunes E, Zanesco A. Exercise training improves relaxation response and SOD-1 expression in aortic and mesenteric rings from high caloric diet-fed rats. BMC Physiol 8: 12, 2008.
13. Derby CA, Mohr BA, Goldstein I, Feldman HA, Johannes CB, McKinlay JB. Modifiable risk factors and erectile dysfunction: can lifestyle changes modify risk? Urology 56: 302-306, 2000.
14. Esposito K, Giugliano D. Obesity, the metabolic syndrome, and sexual dysfunction. Int J Impot Res 17: 391-398, 2005.
15. Esposito K, Giugliano F, Di Palo C, Giugliano G, Marfella R, D'Andrea F, D'Armiento M, Giugliano D. Effect of lifestyle changes on erectile dysfunction in obese men. JAMA 291: 2978-2984, 2004.
16. Finucane MM, Stevens GA, Cowan MJ, Danaei G, Lin JK, Paciorek CJ, Singh GM, Gutierrez HR, Lu Y, Bahalim AN, Farzadfar F, Riley LM, Ezzati M. Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating Group (Body Mass Index). National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet 377: 557-567, 2011.
17. Fisher-Wellman KH, Mattox TA, Thayne K, Katunga LA, La Favor JD, Neufer PD, Hickner RC, Wingard CJ, Anderson EJ. Novel role for thioredoxin reductase-2 in mitochondrial redox adaptations to obesogenic diet and exercise in heart and skeletal muscle. J Physiol In press.
18. Frasier CR, Moukdar F, Patel HD, Sloan RC, Stewart LM, Alleman RJ, La Favor JD, Brown DA. Redox-dependent increases in glutathione reductase and exercise preconditioning: role of NADPH oxidase and mitochondria. Cardiovasc Res 98: 47-55, 2013.
19. Galili O, Versari D, Sattler KJ, Olson ML, Mannheim D, McConnell JP, Chade AR, Lerman LO, Lerman A. Early experimental obesity is associated with coronary endothelial dysfunction and oxidative stress. Am J Physiol Heart Circ Physiol 292: H904-H911, 2007.
20. Gao X, Belmadani S, Picchi A, Xu X, Potter BJ, Tewari-Singh N, Capobianco S, Chilian WM, Zhang C. Tumor necrosis factor-alpha induces endothelial dysfunction in Lepr(db) mice. Circulation 115: 245-254, 2007.
21. Glina S, Sharlip ID, Hellstrom WJ. Modifying risk factors to prevent and treat erectile dysfunction. J Sex Med 10: 115-119, 2012.
22. Guzik TJ, Mussa S, Gastaldi D, Sadowski J, Ratnatunga C, Pillai R, Channon KM. Mechanisms of increased vascular superoxide production in human diabetes mellitus: role of NAD(P)H oxidase and endothelial nitric oxide synthase. Circulation 105: 1656-1662, 2002.
23. Guzik TJ, Sadowski J, Guzik B, Jopek A, Kapelak B, Przybylowski P, Wierzbicki K, Korbut R, Harrison DG, Channon KM. Coronary artery superoxide production and Nox isoform expression in human coronary artery disease. Arterioscler Thromb Vasc Biol 26: 333-339, 2006.
24. Hannan JL, Maio MT, Komolova M, Adams MA. Beneficial impact of exercise and obesity interventions on erectile function and its risk factors. J Sex Med 6 Suppl 3: 254-261, 2009.
25. Haram PM, Adams V, Kemi OJ, Brubakk AO, Hambrecht R, Elling-sen Ø, Wisløff U. Time-course of endothelial adaptation following acute and regular exercise. Eur J Cardiovasc Prev Rehabil 13: 585-591, 2006.
26. Haram PM, Kemi OJ, Lee SJ, Bendheim MØ, Al-Share QY, Waldum HL, Gilligan LJ, Koch LG, Britton SL, Najjar SM, Wisløff U. Aerobic interval training vs. continuous moderate exercise in the metabolic syndrome of rats artificially selected for low aerobic capacity. Cardiovasc Res 81: 723-732, 2009.
27. Heumüller S, Wind S, Barbosa-Sicard E, Schmidt HH, Busse R, Schröder K, Brandes RP. Apocynin is not an inhibitor of vascular NADPH oxidases but an antioxidant. Hypertension 51: 211-217, 2008.
28. Høydal MA, Wisløff U, Kemi OJ, Ellingsen O. Running speed and maximal oxygen uptake in rats and mice: practical implications for exercise training. Eur J Cardiovasc Prev Rehabil 14: 753-760, 2007.
29. Hsiao W, Shrewsberry AB, Moses KA, Johnson TV, Cai AW, Stuhl-dreher P, Dusseault B, Ritenour CWM. Exercise is associated with better erectile function in men under 40 as evaluated by the international index of erectile function. J Sex Med 9: 524-530, 2012.
30. Jackson G, Montorsi P, Adams MA, Anis T, El-Sakka A, Miner M, Vlachopoulos C, Kim E. Cardiovascular aspects of sexual medicine. J Sex Med 7: 1608-1626, 2010.
31. Jackson G, Padley S. Erectile dysfunction and silent coronary artery disease: abnormal computed tomography coronary angiogram in the presence of normal exercise ECGs. Int J Clin Pract 62: 973-976, 2008.
32. Janiszewski PM, Janssen I, Ross R. Abdominal obesity and physical inactivity are associated with erectile dysfunction independent of body mass index. J Sex Med 6: 1990-1998, 2009.
33. Jin L, Lagoda G, Leite R, Webb RC, Burnett AL. NADPH oxidase activation: a mechanism of hypertension-associated erectile dysfunction. J Sex Med 5: 544-551, 2008.
34. Jo H, Otani H, Jo F, Shimazu T, Okazaki T, Yoshioka K, Fujita M, Kosaki A, Iwasaka T. Inhibition of nitric oxide synthase uncoupling by sepiapterin improves left ventricular function in streptozotocin-induced diabetic mice. Clin Exp Pharmacol Physiol 38: 485-493, 2011.
35. Joyner MJ, Green DJ. Exercise protects the cardiovascular system: effects beyond traditional risk factors. J Physiol 587: 5551-5558, 2009.
36. La Favor JD, Anderson EJ, Hickner RC, Wingard CJ. Erectile dysfunction precedes coronary artery endothelial dysfunction in rats fed a high-fat, high-sucrose, Western pattern diet. J Sex Med 10: 694-703, 2013.
37. Laursen JB, Somers M, Kurz S, McCann L, Warnholtz A, Freeman BA, Tarpey M, Fukai T, Harrison DG. Endothelial regulation of vasomotion in ApoE-deficient mice: implications for interactions between peroxynitrite and tetrahydrobiopterin. Circulation 103: 1282-1288, 2001.
38. Long T, Liu G, Wang Y, Chen Y, Zhang Y, Qin D. TNF-a, erectile dysfunction, and NADPH oxidase-mediated ROS generation in corpus cavernosum in high-fat diet/streptozotocin-induced diabetic rats. J Sex Med 9: 1801-1814, 2012.
39. Meldrum DR, Gambone JC, Morris MA, Esposito K, Giugliano D, Ignarro LJ. Lifestyle and metabolic approaches to maximizing erectile and vascular health. Int J Impot Res 24: 61-68, 2012.
40. Montorsi F, Briganti A, Salonia A, Rigatti P, Margonato A, Macchi A, Galli S, Ravagnani PM, Montorsi P. Erectile dysfunction prevalence, time of onset and association with risk factors in 300 consecutive patients with acute chest pain and angiographically documented coronary artery disease. Eur Urol 44: 360-364, 2003.
41. Munk PS, Staal EM, Butt N, Isaksen K, Larsen AI. High-intensity interval training may reduce in-stent restenosis following percutaneous coronary intervention with stent implantation: a randomized controlled trial evaluating the relationship to endothelial function and inflammation. Am Heart J 158: 734-741, 2009.
42. Musicki B, Liu T, Lagoda GA, Strong TD, Sezen SF, Johnson JM, Burnett AL. Hypercholesterolemia-induced erectile dysfunction: endothelial nitric oxide synthase (eNOS) uncoupling in the mouse penis by NAD(P)H oxidase. J Sex Med 7: 3023-3032, 2010.
43. Musicki B, Liu T, Strong T, Jin L, Laughlin MH, Turk JR, Burnett AL. Low-fat diet and exercise preserve eNOS regulation and endothelial function in the penis of early atherosclerotic pigs: a molecular analysis. J Sex Med 5: 552-561, 2008.
44. Park Y, Booth FW, Lee S, Laye MJ, Zhang C. Physical activity opposes coronary vascular dysfunction induced during high fat feeding in mice. J Physiol 590: 4255-4268, 2012.
45. Picchi A, Gao X, Belmadani S, Potter BJ, Focardi M, Chilian WM, Zhang C. Tumor necrosis factor-alpha induces endothelial dysfunction in the prediabetic metabolic syndrome. Circ Res 99: 69-77, 2006.
46. Popkin BM, Adair LS, Ng SW. Global nutrition transition and the pandemic of obesity in developing countries. Nutr Rev 70: 3-21, 2012.
47. Prieto D. Physiological regulation of penile arteries and veins. Int J Impot Res 20: 17-29, 2008.
48. Sánchez A, Contreras C, Martínez MP, Climent B, Benedito S, Garcia-Sacristán A, Hernández M, Prieto D. Role of neural NO synthase (nNOS) uncoupling in the dysfunctional nitrergic vasorelaxation of penile arteries from insulin-resistant obese Zucker rats. PLos One 7: e36027, 2012.
49. Shang T, Kotamraju S, Kalivendi SV, Hillard CJ, Kalyanaraman B. 1-Methyl-4-phenylpyridinium-induced apoptosis in cerebellar granule neurons is mediated by transferrin receptor iron-dependent depletion of tetrahydrobiopterin and neuronal nitric-oxide synthase-derived superoxide. J Biol Chem 279: 19099-19112, 2004.
50. Shukla N, Jones R, Persad R, Angelini GD, Jeremy JY. Effect of sildenafil citrate and a nitric oxide donating sildenafil derivative, NCX 911, on cavernosal relaxation and superoxide formation in hypercholes-terolaemic rabbits. Eur J Pharmacol 517: 224-231, 2005.
51. Stolk J, Hiltermann TJ, Dijkman JH, Verhoeven AJ. Characteristics of the inhibition of NADPH oxidase activation in neutrophils by apocynin, a methoxy-substituted catechol. Am J Respir Cell Mol Biol 11: 95-102, 1994.
52. Sun MW, Zhong MF, Gu J, Qian FL, Gu JZ, Chen H. Effects of different levels of exercise volume on endothelium-dependent vasodilation: roles of nitric oxide synthase and heme oxygenase. Hypertens Res 31: 805-816, 2008.
53. Suresh S, Prakash S. Effect of Mucuana pruriens (Linn.) on oxidative stress-induced structural alteration of corpus cavernosum in streptozoto-cin-induced diabetic rat. J Sex Med 8: 1943-1956, 2011.
54. Thompson IM, Tangen CM, Goodman PJ, Probstfield JL, Moinpoiur CM, Coltman CA. Erectile dysfunction and subsequent cardiovascular disease. JAMA 294: 2996-3002, 2005.
55. Thompson MA, Henderson KK, Woodman CR, Turk JR, Rush JW, Price E, Laughlin MH. Exercise preserves endothelium-dependent relaxation in coronary arteries of hypercholesterolemic male pigs. J Appl Physiol 96: 1114-1126, 2004.
56. Tjønna AE, Lee SJ, Rognmo Ø, Stolen TO, Bye A, Haram PM, Loennechen JP, Al-Share QY, Skogvoll E, Slørdahl AT, Kemi OJ, Najjar SM, Wisløff U. Aerobic interval training versus continuous moderate exercise as a treatment for the metabolic syndrome: a pilot study. Circulation 118: 346-354, 2008.
57. Tsutsui M, Milstien S, Katusic ZS. Effect of tetrahydrobiopterin on endothelial function in canine middle cerebral arteries. Circ Res 79: 336-342, 1996.
58. Vásquez-Vivar J, Duquaine D, Whitsett J, Kalyanaraman B, Rajago-palan S. Altered tetrahydrobiopterin metabolism in atherosclerosis: implications for use of oxidized tetrahydrobiopterin analogues and thiol antioxidants. Arterioscler Thromb Vasc Biol 22: 1655-1661, 2002.
59. Vásquez-Vivar J, Martasek P, Whitsett J, Joseph J, Kalyanaraman B. The ratio between tetrahydrobiopterin and oxidized tetrahydrobiopterin analogues controls superoxide release from endothelial nitric oxide syn-thase: an EPR spin trapping study. Biochem J 362: 733-739, 2002.
60. Vlachopoulos C, Jackson G, Stefanadis C, Montorsi P. Erectile dysfunction in the cardiovascular patient. Eur Heart J In press.
61. Vlachopoulos CV, Terentes-Printzios DG, Ioakeimidis NK, Aznaou-ridis KA, Stefanadis CI. Prediction of cardiovascular events and all-cause mortality with erectile dysfunction: a systemic review and meta-analysis of cohort studies. Circ Cardiovasc Qual Outcomes 6: 99-109, 2013.
62. Vladic N, Ge ZD, Leucker T, Brzezinska AK, Du JH, Shi Y, Warltier DC, Pratt PF Jr, Kersten JR. Decreased tetrahydrobiopterin and disrupted association of Hsp90 with eNOS by hyperglycemia impair myocardial ischemic preconditioning. Am J Physiol Heart Circ Physiol 301: H2130-H2139, 2011.
63. Widlansky ME, Gutterman DD. Regulation of endothelial function by mitochondrial reactive oxygen species. Antioxid Redox Signal 15: 1517-1530, 2011.
64. Wingard C, Fulton D, Husain S. Altered penile vascular reactivity and erection in the Zucker obese-diabetic rat. J Sex Med 4: 348-363, 2007.
65. Wisløff U, Helgerud J, Kemi OJ, Ellingsen O. Intensity-controlled treadmill running in rats: VO2max and cardiac hypertrophy. Am J Physiol Heart Circ Physiol 280: H1301-H1310, 2001.
66. Wisløff U, Støylen A, Loennechen JP, Bruvold M, Rognmo Ø, Haram PM, Tjønna AE, Helgerud J, Slørdahl SA, Lee SJ, Videm V, Bye A, Smith GL, Najjar SM, Ellingsen Ø, Skjaerpe T. Superior cardiovascular effect of aerobic interval training versus moderate continuous training in heart failure patients: a randomized study. Circulation 115: 3086-3094, 2007.
67. Yamashita N, Hoshida S, Otsu K, Asahi M, Kuzuya T, Hori M. Exercise provides direct biphasic cardioprotection via manganese superoxide dismutase activation. J Exp Med 189: 1699-1706, 1999.