Diminazene Protects Corpus Cavernosum Against Hypercholesterolemia-Induced Injury

Journal of Sexual Medicine

Volumn 12, Issue 2, 2015, Pages 289-302

  Fraga Silva, Rodrigo A ^a   Costa Fraga, Fabiana P ^a   Montecucco, Fabrizio ^b,c   Sturny, Mikael ^a   Faye, Younoss ^a   Mach, François ^b   Pelli, Graziano ^b   Shenoy, Vinayak ^d   da Silva, Rafaela F ^e   Raizada, Mohan K ^d   Santos, Robson A S ^e   Stergiopulos, Nikolaos ^a  

^a EPFL   (Switzerland)

^b GENEVA UNIVERSITY HOSPITALS   (Switzerland)

^c UNIVERSITY OF GENOA   (Italy)

^d UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

^e FEDERAL UNIVERSITY OF MINAS GERAIS   (Brazil)

Author keywords

Angiotensin II; Angiotensin (1 7); Angiotensin converting enzyme 2; Erectile dysfunction; Hypercholesterolemia

Indexed keywords

ANGIOTENSIN CONVERTING ENZYME 2; COLLAGEN; DIMINAZENE ACETURATE; ENDOTHELIAL NITRIC OXIDE SYNTHASE; NEURONAL NITRIC OXIDE SYNTHASE; NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; ANGIOTENSIN I; ANGIOTENSIN I (1-7); APOLIPOPROTEIN E; DIMINAZENE; DIPEPTIDYL CARBOXYPEPTIDASE; NITRIC OXIDE; PEPTIDE FRAGMENT;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; CORPUS CAVERNOSUM; DOWN REGULATION; DRUG BIOAVAILABILITY; ENDOTHELIUM CELL; ENZYME ACTIVATION; HYPERCHOLESTEROLEMIA; MALE; MOUSE; NONHUMAN; PENIS INJURY; PRIORITY JOURNAL; PROTEIN EXPRESSION; SMOOTH MUSCLE; ANALOGS AND DERIVATIVES; ANIMAL; COMPLICATION; DRUG EFFECTS; ERECTILE DYSFUNCTION; KNOCKOUT MOUSE; METABOLISM; PATHOPHYSIOLOGY; PENIS; PENIS ERECTION;

ANGIOTENSIN I; ANIMALS; APOLIPOPROTEINS E; DIMINAZENE; DOWN-REGULATION; ERECTILE DYSFUNCTION; HYPERCHOLESTEROLEMIA; MALE; MICE; MICE, KNOCKOUT; NADPH OXIDASE; NITRIC OXIDE; NITRIC OXIDE SYNTHASE TYPE I; NITRIC OXIDE SYNTHASE TYPE III; PENILE ERECTION; PENIS; PEPTIDE FRAGMENTS; PEPTIDYL-DIPEPTIDASE A; REACTIVE OXYGEN SPECIES;

EID: 84922561378     PISSN: 17436095     EISSN: 17436109     Source Type: Journal    
DOI: 10.1111/jsm.12757     Document Type: Article

References (59)

1. Ma TK, Kam KK, Yan BP, Lam YY. Renin-angiotensin-aldosterone system blockade for cardiovascular diseases: Current status. Br J Pharmacol 2010;160:1273-1292.
2. Schiffrin EL. Vascular and cardiac benefits of angiotensin receptor blockers. Am J Med 2002;113:409-418.
3. Fraga-Silva RA, Ferreira AJ, Dos Santos RA. Opportunities for targeting the Angiotensin-converting enzyme 2/angiotensin-(1-7)/mas receptor pathway in hypertension. Curr Hypertens Rep 2013;15:31-38.
4. Becker AJ, Uckert S, Stief CG, Scheller F, Knapp WH, Hartmann U, Jonas U. Plasma levels of angiotensin II during different penile conditions in the cavernous and systemic blood of healthy men and patients with erectile dysfunction. Urology 2001;58:805-810.
5. Becker AJ, Uckert S, Stief CG, Truss MC, Machtens S, Scheller F, Knapp WH, Hartmann U, Jonas U. Possible role of bradykinin and angiotensin II in the regulation of penile erection and detumescence. Urology 2001;57:193-198.
6. da Costa Goncalves AC, Fraga-Silva RA, Leite R, Santos RA. AVE 0991, a non-peptide Mas-receptor agonist, facilitates penile erection. Exp Physiol 2013;98:850-855.
7. da Costa Goncalves AC, Leite R, Fraga-Silva RA, Pinheiro SV, Reis AB, Reis FM, Touyz RM, Webb RC, Alenina N, Bader M, Santos RA. Evidence that the vasodilator angiotensin-(1-7)-Mas axis plays an important role in erectile function. Am J Physiol Heart Circ Physiol 2007;293:H2588-2596.
8. Kifor I, Williams GH, Vickers MA, Sullivan MP, Jodbert P, Dluhy RG. Tissue angiotensin II as a modulator of erectile function. I. Angiotensin peptide content, secretion and effects in the corpus cavernosum. J Urol 1997;157:1920-1925.
9. Yousif MH, Kehinde EO, Benter IF. Different responses to angiotensin-(1-7) in young, aged and diabetic rabbit corpus cavernosum. Pharmacol Res 2007;56:209-216.
10. Fraga-Silva RA, Montecucco F, Mach F, Santos RA, Stergiopulos N. Pathophysiological role of the renin-angiotensin system on erectile dysfunction. Eur J Clin Invest 2013;43:978-985.
11. Park JK, Kim SZ, Kim SH, Park YK, Cho KW. Renin angiotensin system in rabbit corpus cavernosum: Functional characterization of angiotensin II receptors. J Urol 1997;158:653-658.
12. Jin L, Lagoda G, Leite R, Webb RC, Burnett AL. NADPH oxidase activation: A mechanism of hypertension-associated erectile dysfunction. J Sex Med 2008;5:544-551.
13. Fraga-Silva RA, Da Silva DG, Montecucco F, Mach F, Stergiopulos N, da Silva RF, Santos RA. The angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas receptor axis: A potential target for treating thrombotic diseases. Thromb Haemost 2012;108:1089-1096.
14. Vickers C, Hales P, Kaushik V, Dick L, Gavin J, Tang J, Godbout K, Parsons T, Baronas E, Hsieh F, Acton S, Patane M, Nichols A, Tummino P. Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase. J Biol Chem 2002;277:14838-14843.
15. Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem 2000;275:33238-33243.
16. Hernandez Prada JA, Ferreira AJ, Katovich MJ, Shenoy V, Qi Y, Santos RA, Castellano RK, Lampkins AJ, Gubala V, Ostrov DA, Raizada MK. Structure-based identification of small-molecule angiotensin-converting enzyme 2 activators as novel antihypertensive agents. Hypertension 2008;51:1312-1317.
17. Fraga-Silva RA, Costa-Fraga FP, Murca TM, Moraes PL, Martins Lima A, Lautner RQ, Castro CH, Soares CM, Borges CL, Nadu AP, Oliveira ML, Shenoy V, Katovich MJ, Santos RA, Raizada MK, Ferreira AJ. Angiotensin-converting enzyme 2 activation improves endothelial function. Hypertension 2013;61:1233-1238.
18. Fraga-Silva RA, Sorg BS, Wankhede M, Dedeugd C, Jun JY, Baker MB, Li Y, Castellano RK, Katovich MJ, Raizada MK, Ferreira AJ. ACE2 activation promotes antithrombotic activity. Mol Med 2010;16:210-215.
19. Ferreira AJ, Shenoy V, Qi Y, Fraga-Silva RA, Santos RA, Katovich MJ, Raizada MK. Angiotensin-converting enzyme 2 activation protects against hypertension-induced cardiac fibrosis involving extracellular signal-regulated kinases. Exp Physiol 2011;96:287-294.
20. Shenoy V, Gjymishka A, Jarajapu YP, Qi Y, Afzal A, Rigatto K, Ferreira AJ, Fraga-Silva RA, Kearns P, Douglas JY, Agarwal D, Mubarak KK, Bradford C, Kennedy WR, Jun JY, Rathinasabapathy A, Bruce E, Gupta D, Cardounel AJ, Mocco J, Patel JM, Francis J, Grant MB, Katovich MJ, Raizada MK. Diminazene attenuates pulmonary hypertension and improves angiogenic progenitor cell functions in experimental models. Am J Respir Crit Care Med 2013;187:648-657.
21. Qi Y, Zhang J, Cole-Jeffrey CT, Shenoy V, Espejo A, Hanna M, Song C, Pepine CJ, Katovich MJ, Raizada MK. Diminazene aceturate enhances angiotensin-converting enzyme 2 activity and attenuates ischemia-induced cardiac pathophysiology. Hypertension 2013;62:746-752.
22. Mecca AP, Regenhardt RW, O'Connor TE, Joseph JP, Raizada MK, Katovich MJ, Sumners C. Cerebroprotection by angiotensin-(1-7) in endothelin-1-induced ischaemic stroke. Exp Physiol 2011;96:1084-1096.
23. Foureaux G, Nogueira JC, Nogueira BS, Fulgencio GO, Menezes GB, Fernandes SO, Cardoso VN, Fernandes RS, Oliveira GP, Franca JR, Faraco AA, Raizada MK, Ferreira AJ. Antiglaucomatous effects of the activation of intrinsic Angiotensin-converting enzyme 2. Invest Ophthalmol Vis Sci 2013;54:4296-4306.
24. Rigatto K, Casali KR, Shenoy V, Katovich MJ, Raizada MK. Diminazene aceturate improves autonomic modulation in pulmonary hypertension. Eur J Pharmacol 2013;713:89-93.
25. Xie D, Odronic SI, Wu F, Pippen AM, Donatucci CF, Annex BH. A mouse model of hypercholesterolemia-induced erectile dysfunction. J Sex Med 2007;4(4 Pt 1):898-907.
26. Schlimmer N, Kratz M, Bohm M, Baumhakel M. Telmisartan, ramipril and their combination improve endothelial function in different tissues in a murine model of cholesterol-induced atherosclerosis. Br J Pharmacol 2011;163:804-814.
27. Fraga-Silva RA, Costa-Fraga FP, Montecucco F, Faye Y, Savergnini SQ, Lenglet S, Mach F, Steffens S, Stergiopulos N, dos Santos RA, da Silva RF. Treatment with CB2 agonist JWH-133 reduces histological features associated with erectile dysfunction in hypercholesterolemic mice. Clin Dev Immunol 2013;2013:263846.
28. 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 2010;7:3023-3032.
29. McKinlay JB. The worldwide prevalence and epidemiology of erectile dysfunction. Int J Impot Res 2000;12(suppl 4):S6-11.
30. Chung E, De Young L, Brock GB. Investigative models in erectile dysfunction: A state-of-the-art review of current animal models. J Sex Med 2011;8:3291-3305.
31. Fraga-Silva RA, Costa-Fraga FP, Savergnini SQ, De Sousa FB, Montecucco F, da Silva D, Sinisterra RD, Mach F, Stergiopulos N, da Silva RF, Santos RA. An oral formulation of angiotensin-(1-7) reverses corpus cavernosum damages induced by hypercholesterolemia. J Sex Med 2013;10:2430-2442.
32. Yesilli C, Yaman O, Anafarta K. Effect of experimental hypercholesterolemia on cavernosal structures. Urology 2001;57:1184-1188.
33. Fraga-Silva RA, Costa-Fraga FP, Faye Y, Sturny M, Santos RA, da Silva RF, Stergiopulos N. An increased arginase activity is associated with corpus cavernosum impairment induced by hypercholesterolemia. J Sex Med 2014;11:1173-1181.
34. Maganto-Garcia E, Tarrio M, Lichtman AH. Mouse models of atherosclerosis. In: Coligan JE, Bierer BE, Margulies DH, Shevach EM and Strober W, eds. Current protocols in immunology. John Wiley & Sons, New York, NY; 2012:11-23. Chapter 15:Unit 15 24.
35. Schlimmer N, Kratz M, Bohm M, Baumhakel M. Telmisartan, ramipril and their combination improve endothelial function in different tissues in a murine model of cholesterol-induced atherosclerosis. Br J Pharmacol 2011;163:804-814.
36. Fraga-Silva R, Costa-Fraga F, Savergnini S, De Sousa F, Montecucco F, da Silva D, Sinisterra R, Mach F, Stergiopulos N, da Silva R, Santos RA. An oral formulation of angiotensin-(1-7) protects against hypercholesterolemic-induced corpus cavernosum damages. J Sex Med 2012;9(suppl 4):231-232. In: World Meeting on Sexual Medicine 2012: 2012; Chicago, USA.
37. Baumhakel M, Custodis F, Schlimmer N, Laufs U, Bohm M. Improvement of endothelial function of the corpus cavernosum in apolipoprotein E knockout mice treated with irbesartan. J Pharmacol Exp Ther 2008;327:692-698.
38. Shenoy V, Ferreira AJ, Qi Y, Fraga-Silva RA, Diez-Freire C, Dooies A, Jun JY, Sriramula S, Mariappan N, Pourang D, Venugopal CS, Francis J, Reudelhuber T, Santos RA, Patel JM, Raizada MK, Katovich MJ. The angiotensin-converting enzyme 2/angiogenesis-(1-7)/Mas axis confers cardiopulmonary protection against lung fibrosis and pulmonary hypertension. Am J Respir Crit Care Med 2010;182:1065-1072.
39. Wang Y, Tikellis C, Thomas MC, Golledge J. Angiotensin converting enzyme 2 and atherosclerosis. Atherosclerosis 2013;226:3-8.
40. Unger T. The role of the renin-angiotensin system in the development of cardiovascular disease. Am J Cardiol 2002;89(2A):3A-9A, discussion 10A.
41. Nicholls MG, Richards AM, Agarwal M. The importance of the renin-angiotensin system in cardiovascular disease. J Hum Hypertens 1998;12:295-299.
42. Iwamoto Y, Song K, Takai S, Yamada M, Jin D, Sakaguchi M, Ueda H, Katsuoka Y, Miyazaki M. Multiple pathways of angiotensin I conversion and their functional role in the canine penile corpus cavernosum. J Pharmacol Exp Ther 2001;298:43-48.
43. Ferreira AJ, Santos RA. Cardiovascular actions of angiotensin-(1-7). Braz J Med Biol Res 2005;38:499-507.
44. Ferreira AJ, Santos RA, Bradford CN, Mecca AP, Sumners C, Katovich MJ, Raizada MK. Therapeutic implications of the vasoprotective axis of the renin-angiotensin system in cardiovascular diseases. Hypertension 2010;55:207-213.
45. Bader M, Ganten D. Update on tissue renin-angiotensin systems. J Mol Med 2008;86:615-621.
46. Ferreira AJ, Murca TM, Fraga-Silva RA, Castro CH, Raizada MK, Santos RA. New cardiovascular and pulmonary therapeutic strategies based on the Angiotensin-converting enzyme 2/angiotensin-(1-7)/mas receptor axis. Int J Hypertens 2012;2012:147825.
47. Fraga-Silva RA, Ferreira AJ, Dos Santos RA. Opportunities for targeting the angiotensin-converting enzyme 2/angiotensin-(1-7)/mas receptor pathway in hypertension. Curr Hypertens Rep 2013;15:31-38.
48. Bivalacqua TJ, Usta MF, Champion HC, Kadowitz PJ, Hellstrom WJ. Endothelial dysfunction in erectile dysfunction: Role of the endothelium in erectile physiology and disease. J Androl 2003;24(6 suppl):S17-37.
49. Kim SC, Kim IK, Seo KK, Baek KJ, Lee MY. Involvement of superoxide radical in the impaired endothelium-dependent relaxation of cavernous smooth muscle in hypercholesterolemic rabbits. Urol Res 1997;25:341-346.
50. Azadzoi KM, Saenz de Tejada I. Hypercholesterolemia impairs endothelium-dependent relaxation of rabbit corpus cavernosum smooth muscle. J Urol 1991;146:238-240.
51. Touyz RM, Berry C. Recent advances in angiotensin II signaling. Braz J Med Biol Res 2002;35:1001-1015.
52. Rabelo LA, Alenina N, Bader M. ACE2-angiotensin-(1-7)-Mas axis and oxidative stress in cardiovascular disease. Hypertens Res 2011;34:154-160.
53. Xu P, Costa-Goncalves AC, Todiras M, Rabelo LA, Sampaio WO, Moura MM, Santos SS, Luft FC, Bader M, Gross V, Alenina N, Santos RA. Endothelial dysfunction and elevated blood pressure in MAS gene-deleted mice. Hypertension 2008;51:574-580.
54. Burnett AL, Lowenstein CJ, Bredt DS, Chang TS, Snyder SH. Nitric oxide: A physiologic mediator of penile erection. Science 1992;257:401-403.
55. Beyer AM, Guo DF, Rahmouni K. Prolonged treatment with angiotensin 1-7 improves endothelial function in diet-induced obesity. J Hypertens 2013;31:730-738.
56. Faria-Silva R, Duarte FV, Santos RA. Short-term angiotensin(1-7) receptor MAS stimulation improves endothelial function in normotensive rats. Hypertension 2005;46:948-952.
57. Cheng C, Tempel D, van Haperen R, van der Baan A, Grosveld F, Daemen MJ, Krams R, de Crom R. Atherosclerotic lesion size and vulnerability are determined by patterns of fluid shear stress. Circulation 2006;113:2744-2753.
58. Zhang C, Zhao YX, Zhang YH, Zhu L, Deng BP, Zhou ZL, Li SY, Lu XT, Song LL, Lei XM, Tang WB, Wang N, Pan CM, Song HD, Liu CX, Dong B, Zhang Y, Cao Y. Angiotensin-converting enzyme 2 attenuates atherosclerotic lesions by targeting vascular cells. Proc Natl Acad Sci U S A 2010;107:15886-15891.
59. Dong B, Zhang C, Feng JB, Zhao YX, Li SY, Yang YP, Dong QL, Deng BP, Zhu L, Yu QT, Liu CX, Liu B, Pan CM, Song HD, Zhang MX, Zhang Y. Overexpression of ACE2 enhances plaque stability in a rabbit model of atherosclerosis. Arterioscler Thromb Vasc Biol 2008;28:1270-1276.