Losartan metabolite EXP3179: An AT1-receptor-independent treatment strategy for patients with the metabolic syndrome?

Hypertension

Volumn 54, Issue 4, 2009, Pages 710-712

  Rossi, Gian Paolo ^a  

^a UNIVERSITY OF PADOVA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

2 BUTYL 4 CHLORO 1 [[2' (1H TETRAZOL 5 YL) 4 BIPHENYLYL]METHYL] 5 IMIDAZOLECARBOXYLIC ACID; ABC TRANSPORTER G1; ANGIOTENSIN 1 RECEPTOR; CD36 ANTIGEN; CHEMOTAXIN; CYCLOOXYGENASE 2; CYTOCHROME P450; DRUG METABOLITE; ENDOTHELIAL NITRIC OXIDE SYNTHASE; EXP 3179; INTERCELLULAR ADHESION MOLECULE 1; IRBESARTAN; LOSARTAN; LOSARTAN POTASSIUM; MESSENGER RNA; MONOCYTE CHEMOTACTIC PROTEIN 1; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PHOSPHATIDYLINOSITOL 3 KINASE; PIOGLITAZONE; PROSTAGLANDIN F2 ALPHA; PROTEIN KINASE B; TELMISARTAN; THROMBOXANE A2; UNCLASSIFIED DRUG;

ADIPOCYTE; AGE DISTRIBUTION; ATHEROSCLEROSIS; BODY MASS; CELL DIFFERENTIATION; CELL MIGRATION; COMORBIDITY; DRUG BLOOD LEVEL; DRUG TARGETING; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; GENE EXPRESSION; GLUCOSE METABOLISM; HUMAN; HYPERTENSION; LIPID METABOLISM; LIPOPHILICITY; METABOLIC SYNDROME X; NOTE; PRIORITY JOURNAL; UPREGULATION;

ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS; CYCLOOXYGENASE 2 INHIBITORS; DINOPROST; HUMANS; INTERCELLULAR ADHESION MOLECULE-1; LOSARTAN; METABOLIC SYNDROME X; PPAR GAMMA; RECEPTOR, ANGIOTENSIN, TYPE 1; THROMBOXANE A2;

EID: 70349686490     PISSN: 0194911X     EISSN: None     Source Type: Journal    
DOI: 10.1161/HYPERTENSIONAHA.109.138883     Document Type: Note

References (16)

1. Goa KL, Wagstaff AJ. Losartan potassium: a review of its pharmacology, clinical efficacy and tolerability in the management of hypertension. Drugs. 1996;51:820-845
2. Sica DA, Gehr TW, Ghosh S. Clinical pharmacokinetics of losartan. Clin Pharmacokinet. 2005;44:797-814
3. Kramer C, Sunkomat J, Witte J, Luchtefeld M, Walden M, Schmidt B, Tsikas D, Boger RH, Forssmann WG, Drexler H, Schieffer B. Angiotensin II receptor-independent antiinflammatory and antiaggregatory properties of losartan: role of the active metabolite EXP3179. Circ Res. 2002;90:770-776
4. Watanabe T, Suzuki J, Yamawaki H, Sharma VK, Sheu SS, Berk BC. Losartan metabolite EXP3179 activates Akt and endothelial nitric oxide synthase via vascular endothelial growth factor receptor-2 in endothelial cells: angiotensin II type 1 receptor-independent effects of EXP3179. Circulation. 2005;112:1798-1805
5. Kappert K, Tsuprykov O, Kaufmann J, Fritzsche J, Ott I, Goebel M, Baehr NI, Haessle PL, Gust R, Fleck E, Unger T, Stawowy P, Kintscher U. Chronic treatment with losartan results in sufficient serum levels of the metabolite EXP3179 for PPAR- activation. Hypertension. 2009;54: 738-743
6. Lee CH, Olson P, Evans RM. Minireview: lipid metabolism, metabolic diseases, and peroxisome proliferator-activated receptors. Endocrinology. 2003;144:2201-2207
7. Savage DB, Tan GD, Acerini CL, Jebb SA, Agostini M, Gurnell M, Williams RL, Umpleby AM, Thomas EL, Bell JD, Dixon AK, Dunne F, Boiani R, Cinti S, Vidal-Puig A, Karpe F, Chatterjee VK, O'Rahilly S. Human metabolic syndrome resulting from dominant-negative mutations in the nuclear receptor peroxisome proliferator-activated receptor--. Diabetes. 2003;52:910-917
8. Staels B, Fruchart JC. Therapeutic roles of peroxisome proliferator-activated receptor agonists. Diabetes. 2005;54:2460-2470 (Pubitemid 41134276)
9. Collins AR, Meehan WP, Kintscher U, Jackson S, Wakino S, Noh G, Palinski W, Hsueh WA, Law RE. Troglitazone inhibits formation of early atherosclerotic lesions in diabetic and nondiabetic low density lipoprotein receptor-deficient mice. Arterioscler Thromb Vasc Biol. 2001;21: 365-371
10. Dormandy JA, Charbonnel B, Eckland DJ, Erdmann E, Massi-Benedetti M, Moules IK, Skene AM, Tan MH, Lefebvre PJ, Murray GD, Standl E, Wilcox RG, Wilhelmsen L, Betteridge J, Birkeland K, Golay A, Heine RJ, Koranyi L, Laakso M, Mokan M, Norkus A, Pirags V, Podar T, Scheen A, Scherbaum W, Schernthaner G, Schmitz O, Skrha J, Smith U, Taton J. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet. 2005;366:1279-1289
11. Benson SC, Pershadsingh HA, Ho CI, Chittiboyina A, Desai P, Pravenec M, Qi N, Wang J, Avery MA, Kurtz TW. Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPAR -modulating activity. Hypertension. 2004;43:993-1002
12. Schupp M, Janke J, Clasen R, Unger T, Kintscher U. Angiotensin type 1 receptor blockers induce peroxisome proliferator-activated receptor- activity. Circulation. 2004;109:2054-2057
13. Schupp M, Lee LD, Frost N, Umbreen S, Schmidt B, Unger T, Kintscher U. Regulation of peroxisome proliferator-activated receptor - activity by losartan metabolites. Hypertension. 2006;47:586-589
14. Wang Y, Chen Z, Liao Y, Mei C, Peng H, Wang M, Guo H, Lu H. Angiotensin II increases the cholesterol content of foam cells via downregulating the expression of ATP-binding cassette transporter A1. Biochem Biophys Res Commun. 2007;353:650-654
15. Moore KJ, Rosen ED, Fitzgerald ML, Randow F, Andersson LP, Altshuler D, Milstone DS, Mortensen RM, Spiegelman BM, Freeman MW. The role of PPAR- in macrophage differentiation and cholesterol uptake. Nat Med. 2001;7:41-47
16. Mogi M, Li JM, Tsukuda K, Iwanami J, Min LJ, Sakata A, Fujita T, Iwai M, Horiuchi M. Telmisartan prevented cognitive decline partly due to PPAR- activation. Biochem Biophys Res Commun. 2008;375:446-449