Mineralocorticoid receptor blocker eplerenone improves endothelial function and inhibits Rho-associated kinase activity in patients with hypertension

Clinical Pharmacology and Therapeutics

Volumn 91, Issue 2, 2012, Pages 289-297

  Fujimura, N ^a   Noma, K ^a   Hata, T ^a   Soga, J ^a   Hidaka, T ^a   Idei, N ^a   Fujii, Y ^a   Mikami, S ^a   Maruhashi, T ^a   Iwamoto, Y ^a   Kihara, Y ^a   Chayama, K ^b   Kato, H ^c   Liao, J K ^d   Higashi, Y ^a,e  

^a HIROSHIMA UNIVERSITY   (Japan)

^b HIROSHIMA UNIVERSITY   (Japan)

^c Ten noz Clinic   (Japan)

^d BRIGHAM AND WOMEN S HOSPITAL   (United States)

^e HIROSHIMA UNIVERSITY HOSPITAL   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

EPLERENONE; GLYCERYL TRINITRATE; LOSARTAN; NIFEDIPINE; RHO KINASE;

ADULT; ARTICLE; CELL MIGRATION; CONTROLLED STUDY; ENDOTHELIUM CELL; ENZYME ACTIVITY; ESSENTIAL HYPERTENSION; FEMALE; FLOW CYTOMETRY; FLOW MEDIATED VASODILATION; FOLLOW UP; HUMAN; HYPOTENSION; LEUKOCYTE; MAJOR CLINICAL STUDY; MALE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SINGLE BLIND PROCEDURE; STEM CELL; VASODILATATION;

ALDOSTERONE ANTAGONISTS; ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS; CALCIUM CHANNEL BLOCKERS; CELL MOVEMENT; ENDOTHELIUM, VASCULAR; FEMALE; HUMANS; HYPERTENSION; LEUKOCYTES; LOSARTAN; MALE; MIDDLE AGED; NIFEDIPINE; NITROGLYCERIN; RHO-ASSOCIATED KINASES; SPIRONOLACTONE; STEM CELLS; VASCULAR ENDOTHELIAL GROWTH FACTOR A; VASODILATION;

EID: 84855979548     PISSN: 00099236     EISSN: 15326535     Source Type: Journal    
DOI: 10.1038/clpt.2011.227     Document Type: Article

References (47)

1. Amano, M. et al. Formation of actin stress fibers and focal adhesions enhanced by Rho-kinase. Science 275, 1308-1311 (1997). (Pubitemid 27114159)
2. Uehata, M. et al. Calcium sensitization of smooth muscle mediated by a Rhoassociated protein kinase in hypertension. Nature 389, 990-994 (1997). (Pubitemid 27485693)
3. Hall, A. Rho GTPases and the actin cytoskeleton. Science 279, 509-514 (1998). (Pubitemid 28067271)
4. Kimura, K. et al. Regulation of the association of adducin with actin filaments by Rho-associated kinase (Rho-kinase) and myosin phosphatase. J. Biol. Chem. 273, 5542-5548 (1998). (Pubitemid 28124020)
5. Sauzeau, V. et al. Cyclic GMP-dependent protein kinase signaling pathway inhibits RhoA-induced Ca2+ sensitization of contraction in vascular smooth muscle. J. Biol. Chem. 275, 21722-21729 (2000).
6. Seasholtz, T.M., Zhang, T., Morissette, M.R., Howes, A.L., Yang, A.H. & Brown, J.H. Increased expression and activity of RhoA are associated with increased DNA synthesis and reduced p27(Kip1) expression in the vasculature of hypertensive rats. Circ. Res. 89, 488-495 (2001). (Pubitemid 34132642)
7. Wehrwein, E.A., Northcott, C.A., Loberg, R.D. & Watts, S.W. Rho/Rho kinase and phosphoinositide 3-kinase are parallel pathways in the development of spontaneous arterial tone in deoxycorticosterone acetate-salt hypertension. J. Pharmacol. Exp. Ther. 309, 1011-1019 (2004). (Pubitemid 38669686)
8. Zeng, Y., Zhuang, S., Gloddek, J., Tseng, C.C., Boss, G.R. & Pilz, R.B. Regulation of cGMP-dependent protein kinase expression by Rho and Kruppel-like transcription factor-4. J. Biol. Chem. 281, 16951-16961 (2006).
9. Masumoto, A., Hirooka, Y., Shimokawa, H., Hironaga, K., Setoguchi, S. & Takeshita, A. Possible involvement of Rho-kinase in the pathogenesis of hypertension in humans. Hypertension 38, 1307-1310 (2001). (Pubitemid 34033407)
10. Hata, T. et al.; ROCK Study Group. Calcium channel blocker and Rhoassociated kinase activity in patients with hypertension. J. Hypertens. 29, 373-379 (2011).
11. Ross, R. Atherosclerosis-an inflammatory disease. N. Engl. J. Med. 340, 115-126 (1999).
12. Lerman, A. & Zeiher, A.M. Endothelial function: cardiac events. Circulation 111, 363-368 (2005). (Pubitemid 40165345)
13. Panza, J.A., Quyyumi, A.A., Brush, J.E. Jr & Epstein, S.E. Abnormal endotheliumdependent vascular relaxation in patients with essential hypertension. N. Engl. J. Med. 323, 22-27 (1990). (Pubitemid 20209468)
14. Taddei, S., Virdis, A., Ghiadoni, L., Magagna, A. & Salvetti, A. Vitamin C improves endothelium-dependent vasodilation by restoring nitric oxide activity in essential hypertension. Circulation 97, 2222-2229 (1998). (Pubitemid 28265383)
15. Higashi, Y. et al. Regular aerobic exercise augments endotheliumdependent vascular relaxation in normotensive as well as hypertensive subjects: role of endothelium-derived nitric oxide. Circulation 100, 1194-1202 (1999). (Pubitemid 29426595)
16. Schiffrin, E.L. & Deng, L.Y. Comparison of effects of angiotensin I-converting enzyme inhibition and beta-blockade for 2 years on function of small arteries from hypertensive patients. Hypertension 25, 699-703 (1995).
17. Higashi, Y. et al. A comparison of angiotensin-converting enzyme inhibitors, calcium antagonists, beta-blockers and diuretic agents on reactive hyperemia in patients with essential hypertension: a multicenter study. J. Am. Coll. Cardiol. 35, 284-291 (2000). (Pubitemid 30125515)
18. Pitt, B. et al. for the Randomized Aldactone Evaluation Study Investigators. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N. Engl. J. Med. 341, 709-717 (1999). (Pubitemid 29407370)
19. Pitt, B. et al.; Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N. Engl. J. Med. 348, 1309-1321 (2003). (Pubitemid 36384098)
20. Zannad, F. et al.; EMPHASIS-HF Study Group. Eplerenone in patients with systolic heart failure and mild symptoms. N. Engl. J. Med. 364, 11-21 (2011).
21. Schiffrin, E.L. Vascular and cardiac benefits of angiotensin receptor blockers. Am. J. Med. 113, 409-418 (2002). (Pubitemid 35230007)
22. Unger, T. The role of the renin-angiotensin system in the development of cardiovascular disease. Am. J. Cardiol. 89, 3A-9A; discussion 10A (2002).
23. Vanhoutte, P.M., Boulanger, C.M., Illiano, S.C., Nagao, T., Vidal, M. & Mombouli, J.V. Endothelium-dependent effects of converting-enzyme inhibitors. J. Cardiovasc. Pharmacol. 22 (suppl. 5), S10-S16 (1993). (Pubitemid 23330003)
24. Creager, M.A. & Roddy, M.A. Effect of captopril and enalapril on endothelial function in hypertensive patients. Hypertension 24, 499-505 (1994). (Pubitemid 24296474)
25. Daemen, M.J., Lombardi, D.M., Bosman, F.T. & Schwartz, S.M. Angiotensin II induces smooth muscle cell proliferation in the normal and injured rat arterial wall. Circ. Res. 68, 450-456 (1991).
26. Sudhir, K., Chou, T.M., Hutchison, S.J. & Chatterjee, K. Coronary vasodilation induced by angiotensin-converting enzyme inhibition in vivo: differential contribution of nitric oxide and bradykinin in conductance and resistance arteries. Circulation 93, 1734-1739 (1996). (Pubitemid 26131351)
27. Hao, L., Kanno, Y., Fukushima, R., Watanabe, Y., Ishida, Y. & Suzuki, H. Effects of eplerenone on heart and kidney in two-kidney, one-clip rats. Am. J. Nephrol. 24, 54-60 (2004). (Pubitemid 38250486)
28. Kobayashi, N. et al. Eplerenone shows renoprotective effect by reducing LOX-1-mediated adhesion molecule, PKCepsilon-MAPK-p90RSK, and Rho-kinase pathway. Hypertension 45, 538-544 (2005). (Pubitemid 40411256)
29. Sanz-Rosa, D. et al. Eplerenone reduces oxidative stress and enhances eNOS in SHR: vascular functional and structural consequences. Antioxid. Redox Signal. 7, 1294-1301 (2005). (Pubitemid 41232527)
30. Nishizaka, M.K., Zaman, M.A., Green, S.A., Renfroe, K.Y. & Calhoun, D.A. Impaired endothelium-dependent flow-mediated vasodilation in hypertensive subjects with hyperaldosteronism. Circulation 109, 2857-2861 (2004). (Pubitemid 38780298)
31. Macdonald, J.E., Kennedy, N. & Struthers, A.D. Effects of spironolactone on endothelial function, vascular angiotensin converting enzyme activity, and other prognostic markers in patients with mild heart failure already taking optimal treatment. Heart 90, 765-770 (2004). (Pubitemid 38813637)
32. Davies, J.I., Band, M., Morris, A. & Struthers, A.D. Spironolactone impairs endothelial function and heart rate variability in patients with type 2 diabetes. Diabetologia 47, 1687-1694 (2004). (Pubitemid 40022402)
33. Joffe, H.V., Kwong, R.Y., Gerhard-Herman, M.D., Rice, C., Feldman, K. & Adler, G.K. Beneficial effects of eplerenone versus hydrochlorothiazide on coronary circulatory function in patients with diabetes mellitus. J. Clin. Endocrinol. Metab. 92, 2552-2558 (2007). (Pubitemid 47037357)
34. Hill, J.M. et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N. Engl. J. Med. 348, 593-600 (2003). (Pubitemid 36204953)
35. Taddei, S., Virdis, A., Ghiadoni, L., Sudano, I. & Salvetti, A. Antihypertensive drugs and reversing of endothelial dysfunction in hypertension. Curr. Hypertens. Rep. 2, 64-70 (2000).
36. Higashi, Y. et al. Angiotensin-converting enzyme inhibition, but not calcium antagonism, improves a response of the renal vasculature to L-arginine in patients with essential hypertension. Hypertension 32, 16-24 (1998). (Pubitemid 28324119)
37. Dahl, B. et al.; LIFE Study Group. Cardiovascular morbidity and mortality in the Losartan Intervention for Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 359, 995-1003 (2002).
38. Miyata, K. et al. Possible involvement of Rho-kinase in aldosterone-induced vascular smooth muscle cell remodeling. Hypertens. Res. 31, 1407-1413 (2008).
39. Doi, T. et al. Aldosterone induces interleukin-18 through endothelin-1, angiotensin II, Rho/Rho-kinase, and PPARs in cardiomyocytes. Am. J. Physiol. Heart Circ. Physiol. 295, H1279-H1287 (2008).
40. Sun, G.P. et al. Involvements of Rho-kinase and TGF-beta pathways in aldosterone-induced renal injury. J. Am. Soc. Nephrol. 17, 2193-2201 (2006).
41. Masumoto, A., Mohri, M., Shimokawa, H., Urakami, L., Usui, M. & Takeshita, A. Suppression of coronary artery spasm by the Rho-kinase inhibitor fasudil in patients with vasospastic angina. Circulation 105, 1545-1547 (2002). (Pubitemid 34297629)
42. Liu, P.Y., Chen, J.H., Lin, L.J. & Liao, J.K. Increased Rho kinase activity in a Taiwanese population with metabolic syndrome. J. Am. Coll. Cardiol. 49, 1619-1624 (2007). (Pubitemid 46551629)
43. Nohria, A. et al. Statins inhibit Rho kinase activity in patients with atherosclerosis. Atherosclerosis 205, 517-521 (2009).
44. Hidaka, T. et al. Increased leukocyte rho kinase (ROCK) activity and endothelial dysfunction in cigarette smokers. Hypertens. Res. 33, 354-359 (2010).
45. Hata, T. et al. Measurement of Rho-associated kinase (ROCK) activity in humans: validity of leukocyte p-MBS/t-MBS in comparison with vascular response to fasudil. Atherosclerosis 214, 117-121 (2011).
46. Dimmeler, S., Dernbach, E. & Zeiher, A.M. Phosphorylation of the endothelial nitric oxide synthase at ser-1177 is required for VEGF-induced endothelial cell migration. FEBS Lett. 477, 258-262 (2000). (Pubitemid 30450177)
47. Nohria, A. et al. Rho kinase inhibition improves endothelial function in human subjects with coronary artery disease. Circ. Res. 99, 1426-1432 (2006). (Pubitemid 44949679)