6β-Hydroxytestosterone, a Cytochrome P450 1B1 Metabolite of Testosterone, Contributes to Angiotensin II-Induced Hypertension and Its Pathogenesis in Male Mice

Hypertension

Volumn 65, Issue 6, 2015, Pages 1279-1287

  Pingili, Ajeeth K ^a   Kara, Mehmet ^a   Khan, Nayaab S ^a   Estes, Anne M ^a   Lin, Zongtao ^b   Li, Wei ^b   Gonzalez, Frank J ^c   Malik, Kafait U ^a  

^a UNIVERSITY OF TENNESSEE COLLEGE OF MEDICINE   (United States)

^b UNIVERSITY OF TENNESSEE COLLEGE OF PHARMACY   (United States)

^c NATIONAL CANCER INSTITUTE   (United States)

Author keywords

castration; CYP1B1 protein; hypertension; oxidative stress

Indexed keywords

16 ALPHA HYDROXYTESTOSTERONE; 6 BETA HYDROXYTESTOSTERONE; ALPHA SMOOTH MUSCLE ACTIN; ANDROGEN RECEPTOR; ANGIOTENSIN 1 RECEPTOR; ANGIOTENSIN 1A RECEPTOR; ANGIOTENSIN II; COLLAGEN; CYTOCHROME P450 1B1; DIPEPTIDYL CARBOXYPEPTIDASE; MAS RECEPTOR; REACTIVE OXYGEN METABOLITE; RECEPTOR; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; TESTOSTERONE DERIVATIVE; TRANSFORMING GROWTH FACTOR BETA; UNCLASSIFIED DRUG; 6 BETA-HYDROXYTESTOSTERONE; CYP1B1 PROTEIN, MOUSE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CASTRATED MALE; CASTRATION; CONTROLLED STUDY; DISEASE ASSOCIATION; ENZYME ACTIVITY; EXPERIMENTAL HYPERTENSION; GENE DISRUPTION; GENE EXPRESSION; HEART MUSCLE FIBROSIS; HEART VENTRICLE HYPERTROPHY; HORMONE BLOOD LEVEL; MALE; MOUSE; NONHUMAN; OXIDATIVE STRESS; PATHOGENESIS; PRIORITY JOURNAL; SYSTOLIC BLOOD PRESSURE; TIME OF FLIGHT MASS SPECTROMETRY; ULTRA PERFORMANCE LIQUID CHROMATOGRAPHY; ANIMAL; CARDIOMEGALY; COMPARATIVE STUDY; DISEASE MODEL; GENE EXPRESSION REGULATION; GENETICS; HYPERTENSION; METABOLISM; PATHOPHYSIOLOGY; RANDOMIZATION; REFERENCE VALUE;

ANGIOTENSIN II; ANIMALS; CARDIOMEGALY; CASTRATION; CYTOCHROME P-450 CYP1B1; DISEASE MODELS, ANIMAL; GENE EXPRESSION REGULATION; HYDROXYTESTOSTERONES; HYPERTENSION; MALE; MICE; RANDOM ALLOCATION; REACTIVE OXYGEN SPECIES; REFERENCE VALUES;

EID: 84937597554     PISSN: 0194911X     EISSN: 15244563     Source Type: Journal    
DOI: 10.1161/HYPERTENSIONAHA.115.05396     Document Type: Article

References (52)

1. Messerli FH, Garavaglia GE, Schmieder RE, Sundgaard-Riise K, Nunez BD, Amodeo C. Disparate cardiovascular findings in men and women with essential hypertension. Ann Intern Med. 1987;107:158-161.
2. Stampfer MJ, Colditz GA, Willett WC, Manson JE, Rosner B, Speizer FE, Hennekens CH. Postmenopausal estrogen therapy and cardiovascular disease. Ten-year follow-up from the nurses health study. N Engl J Med. 1991;325:756-762. doi: 10.1056/NEJM199109123251102.
3. Burt VL, Whelton P, Roccella EJ, Brown C, Cutler JA, Higgins M, Horan MJ, Labarthe D. Prevalence of hypertension in the US adult population. Results from the Third National Health and Nutrition Examination Survey, 1988-1991. Hypertension. 1995;25:305-313.
4. Staessen J, Bulpitt CJ, Fagard R, Lijnen P, Amery A. The influence of menopause on blood pressure. J Hum Hypertens. 1989;3:427-433.
5. Yong LC, Kuller LH, Rutan G, Bunker C. Longitudinal study of blood pressure: changes and determinants from adolescence to middle age. The Dormont High School follow-up study, 1957-1963 to 1989-1990. Am J Epidemiol. 1993;138:973-983.
6. Dubey RK, Oparil S, Imthurn B, Jackson EK. Sex hormones and hypertension. Cardiovasc Res. 2002;53:688-708.
7. Ji H, Zheng W, Wu X, Liu J, Ecelbarger CM, Watkins R, Arnold AP, Sandberg K. Sex chromosome effects unmasked in angiotensin II-induced hypertension. Hypertension. 2010;55:1275-1282. doi: 10.1161/HYPERTENSIONAHA.109.144949.
8. Xue B, Pamidimukkala J, Hay M. Sex differences in the development of angiotensin II-induced hypertension in conscious mice. Am J Physiol Heart Circ Physiol. 2005;288:H2177-H2184. doi: 10.1152/ajpheart.00969.2004.
9. Masubuchi Y, Kumai T, Uematsu A, Komoriyama K, Hirai M. Gonadectomy-induced reduction of blood pressure in adult spontaneously hypertensive rats. Acta Endocrinol (Copenh). 1982;101:154-160.
10. Reckelhoff JF, Zhang H, Srivastava K, Granger JP. Gender differences in hypertension in spontaneously hypertensive rats: role of androgens and androgen receptor. Hypertension. 1999;34(4 pt 2):920-923.
11. Rowland NE, Fregly MJ. Role of gonadal hormones in hypertension in the Dahl salt-sensitive rat. Clin Exp Hypertens A. 1992;14:367-375.
12. Chen YF, Naftilan AJ, Oparil S. Androgen-dependent angiotensinogen and renin messenger RNA expression in hypertensive rats. Hypertension. 1992;19:456-463.
13. Yanes LL, Sartori-Valinotti JC, Iliescu R, Romero DG, Racusen LC, Zhang H, Reckelhoff JF. Testosterone-dependent hypertension and upregulation of intrarenal angiotensinogen in Dahl salt-sensitive rats. Am J Physiol Renal Physiol. 2009;296:F771-F779. doi: 10.1152/ajprenal.90389.2008.
14. Iliescu R, Cucchiarelli VE, Yanes LL, Iles JW, Reckelhoff JF. Impact of androgen-induced oxidative stress on hypertension in male SHR. Am J Physiol Regul Integr Comp Physiol. 2007;292:R731-R735. doi: 10.1152/ajpregu.00353.2006.
15. Meng S, Cason GW, Gannon AW, Racusen LC, Manning RD Jr. Oxidative stress in Dahl salt-sensitive hypertension. Hypertension. 2003;41:1346-1352. doi: 10.1161/01.HYP.0000070028.99408.E8.
16. Holla VR, Adas F, Imig JD, Zhao X, Price E Jr, Olsen N, Kovacs WJ, Magnuson MA, Keeney DS, Breyer MD, Falck JR, Waterman MR, Capdevila JH. Alterations in the regulation of androgen-sensitive Cyp 4a monooxygenases cause hypertension. Proc Natl Acad Sci U S A. 2001;98:5211-5216. doi: 10.1073/pnas.081627898.
17. Wu CC, Schwartzman ML. The role of 20-HETE in androgen-mediated hypertension. Prostaglandins Other Lipid Mediat. 2011;96:45-53. doi: 10.1016/j.prostaglandins.2011.06.006.
18. Korashy HM, El-Kadi AO. The role of aryl hydrocarbon receptor in the pathogenesis of cardiovascular diseases. Drug Metab Rev. 2006;38:411-450. doi: 10.1080/03602530600632063.
19. Jennings BL, Sahan-Firat S, Estes AM, Das K, Farjana N, Fang XR, Gonzalez FJ, Malik KU. Cytochrome P450 1B1 contributes to angiotensin II-induced hypertension and associated pathophysiology. Hypertension. 2010;56:667-674. doi: 10.1161/HYPERTENSIONAHA.110.154518.
20. Jennings BL, Anderson LJ, Estes AM, Yaghini FA, Fang XR, Porter J, Gonzalez FJ, Campbell WB, Malik KU. Cytochrome P450 1B1 contributes to renal dysfunction and damage caused by angiotensin II in mice. Hypertension. 2012;59:348-354. doi: 10.1161/HYPERTENSIONAHA.111.183301.
21. Jennings BL, Estes AM, Anderson LJ, Fang XR, Yaghini FA, Fan Z, Gonzalez FJ, Campbell WB, Malik KU. Cytochrome P450 1B1 gene disruption minimizes deoxycorticosterone acetate-salt-induced hypertension and associated cardiac dysfunction and renal damage in mice. Hypertension. 2012;60:1510-1516. doi: 10.1161/HYPERTENSIONAHA.112.202606.
22. Sahan-Firat S, Jennings BL, Yaghini FA, Song CY, Estes AM, Fang XR, Farjana N, Khan AI, Malik KU. 2,3′, 4,5-Tetramethoxystilbene prevents deoxycorticosterone-salt-induced hypertension: contribution of cytochrome P450 1B1. Am J Physiol Heart Circ Physiol. 2010; 299:1891-1901.
23. Jennings BL, Montanez DE, May ME Jr, Estes AM, Fang XR, Yaghini FA, Kanu A, Malik KU. Cytochrome P450 1B1 contributes to increased blood pressure and cardiovascular and renal dysfunction in spontaneously hypertensive rats. Cardiovasc Drugs Ther. 2014;28:145-161. doi: 10.1007/s10557-014-6510-4.
24. Jennings BL, George LW, Pingili AK, Khan NS, Estes AM, Fang XR, Gonzalez FJ, Malik KU. Estrogen metabolism by cytochrome P450 1B1 modulates the hypertensive effect of angiotensin II in female mice. Hypertension. 2014;64:134-140. doi: 10.1161/HYPERTENSIONAHA.114.03275.
25. Rahman M, Hayes Sutter C, Emmert GL, Sutter TR. Regioselective 2-hydroxylation of 17beta-estradiol by rat cytochrome P4501B1. Toxicol Appl Pharmacol. 2006;216:469-478. doi: 10.1016/j.taap.2006.06.004.
26. Zacharia LC, Dubey RK, Mi Z, Jackson EK. Methylation of 2-hydroxyestradiol in isolated organs. Hypertension. 2003;42:82-87. doi: 10.1161/01.HYP.0000074702.06466.27.
27. Crespi CL, Penman BW, Steimel DT, Smith T, Yang CS, Sutter TR. Development of a human lymphoblastoid cell line constitutively expressing human CYP1B1 cDNA: substrate specificity with model substrates and promutagens. Mutagenesis. 1997;12:83-89.
28. Song J, Wadhwa L, Bejjani BA, OBrien WE. Determination of 3-keto-4-ene steroids and their hydroxylated metabolites catalyzed by recombinant human cytochrome P450 1B1 enzyme using gas chromatography-mass spectrometry with trimethylsilyl derivatization. J Chromatogr B Analyt Technol Biomed Life Sci. 2003;791:127-135.
29. Choudhary D, Jansson I, Stoilov I, Sarfarazi M, Schenkman JB. Metabolism of retinoids and arachidonic acid by human and mouse cytochrome P450 1b1. Drug Metab Dispos. 2004;32:840-847.
30. Hayes CL, Spink DC, Spink BC, Cao JQ, Walker NJ, Sutter TR. 17 betaestradiol hydroxylation catalyzed by human cytochrome P450 1B1. Proc Natl Acad Sci U S A. 1996;93:9776-9781.
31. Sissung TM, Price DK, Sparreboom A, Figg WD. Pharmacogenetics and regulation of human cytochrome P450 1B1: implications in hormone-mediated tumor metabolism and a novel target for therapeutic intervention. Mol Cancer Res. 2006;4:135-150. doi: 10.1158/1541-7786.MCR-05-0101.
32. Papamitsou T, Barlagiannis D, Papaliagkas V, Kotanidou E, Dermentzopoulou-Theodoridou M. Testosterone-induced hypertrophy, fibrosis and apoptosis of cardiac cells-an ultrastructural and immunohistochemical study. Med Sci Monit. 2011;17:BR266-BR273.
33. Thum T, Borlak J. Testosterone, cytochrome P450, and cardiac hypertrophy. FASEB J. 2002;16:1537-1549. doi: 10.1096/fj.02-0138com.
34. Thum T, Borlak J. Cytochrome P450 mono-oxygenase gene expression and protein activity in cultures of adult cardiomyocytes of the rat. Br J Pharmacol. 2000;130:1745-1752. doi: 10.1038/sj.bjp.0703465.
35. Krauser JA, Voehler M, Tseng LH, Schefer AB, Godejohann M, Guengerich FP. Testosterone 1 beta-hydroxylation by human cytochrome P450 3A4. Eur J Biochem. 2004;271:3962-3969. doi: 10.1111/j.1432-1033.2004.04339.x.
36. Sodhi K, Wu CC, Cheng J, Gotlinger K, Inoue K, Goli M, Falck JR, Abraham NG, Schwartzman ML. CYP4A2-induced hypertension is 20-hydroxyeicosatetraenoic acid-and angiotensin II-dependent. Hypertension. 2010;56:871-878. doi: 10.1161/HYPERTENSIONAHA.110.154559.
37. Singh H, Cheng J, Deng H, Kemp R, Ishizuka T, Nasjletti A, Schwartzman ML. Vascular cytochrome P450 4A expression and 20-hydroxyeicosatetraenoic acid synthesis contribute to endothelial dysfunction in androgeninduced hypertension. Hypertension. 2007;50:123-129. doi: 10.1161/HYPERTENSIONAHA.107.089599.
38. Wu CC, Mei S, Cheng J, Ding Y, Weidenhammer A, Garcia V, Zhang F, Gotlinger K, Manthati VL, Falck JR, Capdevila JH, Schwartzman ML. Androgen-sensitive hypertension associates with upregulated vascular CYP4A12-20-HETE synthase. J Am Soc Nephrol. 2013;24:1288-1296. doi: 10.1681/ASN.2012070714.
39. Garcia V, Cheng J, Weidenhammer A, Ding Y, Wu CC, Zhang F, Gotlinger K, Falck JR, Schwartzman ML. Androgen-induced hypertension in angiotensinogen deficient mice: role of 20-HETE and EETS. Prostaglandins Other Lipid Mediat. 2014;S1098-8823:00076-00078. doi: 10.1016/j. prostaglandins.2014.12.001.
40. Letavernier E, Perez J, Bellocq A, Mesnard L, de Castro Keller A, Haymann JP, Baud L. Targeting the calpain/calpastatin system as a new strategy to prevent cardiovascular remodeling in angiotensin II-induced hypertension. Circ Res. 2008;102:720-728. doi: 10.1161/CIRCRESAHA.107.160077.
41. Magee JA, Chang LW, Stormo GD, Milbrandt J. Direct, androgen receptor-mediated regulation of the FKBP5 gene via a distal enhancer element. Endocrinology. 2006;147:590-598. doi: 10.1210/en.2005-1001.
42. Mendelsohn ME, Karas RH. Molecular and cellular basis of cardiovascular gender differences. Science. 2005;308:1583-1587. doi: 10.1126/science.1112062.
43. Ojeda NB, Royals TP, Black JT, Dasinger JH, Johnson JM, Alexander BT. Enhanced sensitivity to acute angiotensin II is testosterone dependent in adult male growth-restricted offspring. Am J Physiol Regul Integr Comp Physiol. 2010;298:R1421-R1427. doi: 10.1152/ajpregu.00096.2010.
44. Chinnathambi V, Blesson CS, Vincent KL, Saade GR, Hankins GD, Yallampalli C, Sathishkumar K. Elevated testosterone levels during rat pregnancy cause hypersensitivity to angiotensin II and attenuation of endothelium-dependent vasodilation in uterine arteries. Hypertension. 2014;64:405-414. doi: 10.1161/HYPERTENSIONAHA.114.03283.
45. Guilluy C, Brégeon J, Toumaniantz G, Rolli-Derkinderen M, Retailleau K, Loufrani L, Henrion D, Scalbert E, Bril A, Torres RM, Offermanns S, Pacaud P, Loirand G. The Rho exchange factor Arhgef1 mediates the effects of angiotensin II on vascular tone and blood pressure. Nat Med. 2010;16:183-190. doi: 10.1038/nm.2079.
46. Song J, Kost CK Jr, Martin DS. Androgens potentiate renal vascular responses to angiotensin II via amplification of the Rho kinase signaling pathway. Cardiovasc Res. 2006;72:456-463. doi: 10.1016/j.cardiores.2006.09.007.
47. Loria AS, Yamamoto T, Pollock DM, Pollock JS. Early life stress induces renal dysfunction in adult male rats but not female rats. Am J Physiol Regul Integr Comp Physiol. 2013;304:R121-R129. doi: 10.1152/ajpregu.00364.2012.
48. Zimmerman MC, Lazartigues E, Lang JA, Sinnayah P, Ahmad IM, Spitz DR, Davisson RL. Superoxide mediates the actions of angiotensin II in the central nervous system. Circ Res. 2002;91:1038-1045.
49. Crowley SD, Gurley SB, Oliverio MI, Pazmino AK, Griffiths R, Flannery PJ, Spurney RF, Kim H-S, Smithies O, Le TH, Coffman TM. Distinct roles for the kidney and systemic tissues in blood pressure regulation. Proc Natl Acad Sci. 2006;103:7985-7990. doi: 10.1073/pnas.0605545103.
50. Guzik TJ, Hoch NE, Brown KA, McCann LA, Rahman A, Dikalov S, Goronzy J, Weyand C, Harrison DG. Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction. J Exp Med. 2007;204:2449-2460. doi: 10.1084/jem.20070657.
51. Muskhelishvili L, Thompson PA, Kusewitt DF, Wang C, Kadlubar FF. In situ hybridization and immunohistochemical analysis of cytochrome P450 1B1 expression in human normal tissues. J Histochem Cytochem. 2001;49:229-236.
52. Heritage AS, Stumpf WE, Sar M, Grant LD. (3-H)-dihydrotestosterone in catecholamine neurons of rat brain stem: combined localization by autoradiography and formaldehyde-induced fluorescence. J Comp Neurol. 1981;200:289-307. doi: 10.1002/cne.902000208.