Effect of angiotensin receptor blockade on endothelial function: focus on olmesartan medoxomil

Carlos Ferrario, Carlos Ferrario

Abstract

Endothelial dysfunction is the common link between cardiovascular disease risk factors and the earliest event in the cascade of incidents that results in target organ damage. Angiotensin II, the terminal pressor effector arm of the renin-angiotensin-aldosterone system, increases blood pressure (BP) by vasoconstriction and sodium and fluid retention, and has a pro-oxidative action that induces endothelial dysfunction and contributes to vascular remodeling. Angiotensin receptor blockers (ARBs) reduce BP and morbidity and mortality in patients with hypertension, ventricular hypertrophy, diabetes mellitus, and renal disease. Olmesartan medoxomil is a long-acting, well-tolerated, effective ARB that prevents or reverses endothelial dysfunction in animal models of atherosclerosis, hypertension, diabetes, nephropathy, and retinopathy. Olmesartan medoxomil, a prodrug of olmesartan approved for the treatment of hypertension, has been shown to ameliorate endothelial dysfunction in patients with hypertension or diabetes. In randomized studies, the drug reduces vascular inflammation and the volume of large atherosclerotic plaques, increases the number of regenerative endothelial progenitor cells in the peripheral circulation, improves endothelium-dependent relaxation, and restores the normal resistance vessel morphology. Importantly, the impact of olmesartan medoxomil on endothelial dysfunction is thought to be independent of BP lowering.

Keywords: angiotensin receptor blocker; atherosclerosis; endothelial dysfunction; hypertension; olmesartan medoxomil.

Figures

Figure 1
Figure 1
Atherosclerotic plaque formation in relationship to Ang II. Reprinted from the Lancet, 369, Schmeider RE, Hilgers KF, Schlaich MP. Renin-angiotensin system and cardiovascular risk, 1208–1219. Copyright © 2007, with permission from Elsevier. Abbreviations: ICAM-1, intercellular adhesion molecule-1; LDL, low-density lipoprotein; LOX-1, lectin-like oxidized low-density lipoprotein receptor-1; MCP-1, monocyte chemoattractant protein-1; MMP, matrix metalloproteinase; NADPH, nicotinamide adenine dinucleotide phosphate; NRB, norbormide; PAI-1, plasminogen activator inhibitor-1; TNF, tumor necrosis factor; VCAM-1, vascular cell adhesion molecule-1; VSMCs, vascular smooth muscle cells.
Figure 2
Figure 2
The renin-angiotensin-aldosterone system. Reproduced with permission from Trask AJ, Ferrario CM. Angiotensin-(1–7): pharmacology and new perspectives in cardiovascular treatments. Cardiovasc Drug Rev. 2007;25(2):162–174. Copyright © 2007. Blackwell Publishing. Abbreviations: ACE, angiotensin-converting enzyme; Ang, angiotensin; AT1R, angiotensin type 1 receptor; AT2R, angiotensin type 2 receptor; NEP, neprilysin; POP, prolyl oligopeptidase; TOP, thimet oligopeptidase.

References

    1. Hardoon SL, Whincup PH, Lennon LT, Wannamethee SG, Capewell S, Morris RW. How much of the recent decline in the incidence of myocardial infarction in British men can be explained by changes in cardiovascular risk factors? Evidence from a prospective population-based study. Circulation. 2008;117(5):598–604.
    1. Kahn R, Robertson RM, Smith R, Eddy D. The impact of prevention on reducing the burden of cardiovascular disease. Circulation. 2008;118(5):576–585.
    1. Perkovic V, Huxley R, Wu Y, Prabhakaran D, MacMahon S. The burden of blood pressure-related disease: a neglected priority for global health. Hypertension. 2007;50(6):991–997.
    1. Coresh J, Selvin E, Stevens LA, et al. Prevalence of chronic kidney disease in the United States. JAMA. 2007;298(17):2038–2047.
    1. Fox CS, Coady S, Sorlie PD, et al. Increasing cardiovascular disease burden due to diabetes mellitus: the Framingham Heart Study. Circulation. 2007;115(12):1544–1550.
    1. Kestenbaum B, Rudser KD, de Boer IH, et al. Differences in kidney function and incident hypertension: The Multi-Ethnic Study of Atherosclerosis. Ann Intern Med. 2008;148(7):501–508.
    1. Munzel T, Sinning C, Post F, Warnholtz A, Schulz E. Pathophysiology, diagnosis and prognostic implications of endothelial dysfunction. Ann Med. 2008;40(3):180–196.
    1. Pahkala K, Heinonen OJ, Lagstrom H, et al. Vascular endothelial function and leisure-time physical activity in adolescents. Circulation. 2008;118(23):2353–2359.
    1. Halcox JP, Schenke WH, Zalos G, et al. Prognostic value of coronary vascular endothelial dysfunction. Circulation. 2002;106(6):653–658.
    1. Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M. Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis. Circulation. 2007;115(4):459–467.
    1. McAllister AS, Atkinson AB, Johnston GD, Hadden DR, Bell PM, McCance DR. Basal nitric oxide production is impaired in offspring of patients with essential hypertension. Clin Sci (Lond) 1999;97(2):141–147.
    1. Schlaich MP, Parnell MM, Ahlers BA, et al. Impaired L-arginine transport and endothelial function in hypertensive and genetically predisposed normotensive subjects. Circulation. 2004;110(24):3680–3686.
    1. Yang Z, Venardos K, Jones E, Morris BJ, Chin-Dusting J, Kaye DM. Identification of a novel polymorphism in the 3’UTR of the L-arginine transporter gene SLC7A1: contribution to hypertension and endothelial dysfunction. Circulation. 2007;115(10):1269–1274.
    1. Zhang C. The role of inflammatory cytokines in endothelial dysfunction. Basic Res Cardiol. 2008;103(5):398–406.
    1. Ferrario CM, Richmond RS, Smith R, Levy P, Strawn WB, Kivlighn S. Renin-angiotensin system as a therapeutic target in managing atherosclerosis. Am J Ther. 2004;11(1):44–53.
    1. Ferrario CM, Strawn WB. Role of the renin-angiotensin-aldosterone system and proinflammatory mediators in cardiovascular disease. Am J Cardiol. 2006;98(1):121–128.
    1. Strawn WB, Dean RH, Ferrario CM. Novel mechanisms linking angiotensin II and early atherogenesis. J Renin Angiotensin Aldosterone Syst. 2000;1(1):11–17.
    1. Strawn WB, Ferrario CM. Mechanisms linking angiotensin II and atherogenesis. Curr Opin Lipidol. 2002;13(5):505–512.
    1. Humphrey JD. Mechanisms of arterial remodeling in hypertension: coupled roles of wall shear and intramural stress. Hypertension. 2008;52(2):195–200.
    1. Abuissa H, Jones PG, Marso SP, O’Keefe JH., Jr Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for prevention of type 2 diabetes: a meta-analysis of randomized clinical trials. J Am Coll Cardiol. 2005;46(5):821–826.
    1. Schupp M, Clemenz M, Gineste R, et al. Molecular characterization of new selective peroxisome proliferator-activated receptor gamma modulators with angiotensin receptor blocking activity. Diabetes. 2005;54(12):3442–3452.
    1. Schupp M, Lee LD, Frost N, et al. Regulation of peroxisome proliferator-activated receptor gamma activity by losartan metabolites. Hypertension. 2006;47(3):586–589.
    1. Engeli S, Bohnke J, Gorzelniak K, et al. Weight loss and the renin-angiotensin-aldosterone system. Hypertension. 2005;45(3):356–362.
    1. Engeli S, Schling P, Gorzelniak K, et al. The adipose-tissue renin-angiotensin-aldosterone system: role in the metabolic syndrome? Int J Biochem Cell Biol. 2003;35(6):807–825.
    1. Sharma AM. Is there a rationale for angiotensin blockade in the management of obesity hypertension? Hypertension. 2004;44(1):12–19.
    1. Sharma AM, Engeli S. The role of renin-angiotensin system blockade in the management of hypertension associated with the cardiometabolic syndrome. J Cardiometab Syndr. 2006;1(1):29–35.
    1. Varagic J, Trask AJ, Jessup JA, Chappell MC, Ferrario CM. New angiotensins. J Mol Med. 2008;86(6):663–671.
    1. Imanishi T, Hano T, Nishio I. Angiotensin II accelerates endothelial progenitor cell senescence through induction of oxidative stress. J Hypertens. 2005;23(1):97–104.
    1. Vasa M, Fichtlscherer S, Aicher A, et al. Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res. 2001;89(1):E1–E7.
    1. Strawn WB, Chappell MC, Dean RH, Kivlighn S, Ferrario CM. Inhibition of early atherogenesis by losartan in monkeys with diet-induced hypercholesterolemia. Circulation. 2000;101(13):1586–1593.
    1. Wassmann S, Czech T, van Eickels M, Fleming I, Bohm M, Nickenig G. Inhibition of diet-induced atherosclerosis and endothelial dysfunction in apolipoprotein E/angiotensin II type 1A receptor double-knockout mice. Circulation. 2004;110(19):3062–3067.
    1. Richmond RS, Tallant EA, Gallagher PE, Ferrario CM, Strawn WB. Angiotensin II stimulates arachidonic acid release from bone marrow stromal cells. J Renin Angiotensin Aldosterone Syst. 2004;5(4):176–182.
    1. Strawn WB, Richmond RS, Ann Tallant E, Gallagher PE, Ferrario CM. Renin-angiotensin system expression in rat bone marrow haematopoietic and stromal cells. Br J Haematol. 2004;126(1):120–126.
    1. Strawn WB, Ferrario CM. Angiotensin II AT1 receptor blockade normalizes CD11b+ monocyte production in bone marrow of hypercholesterolemic monkeys. Atherosclerosis. 2008;196(2):624–632.
    1. Santos RA, Simoes e Silva AC, Maric C, et al. Angiotensin-(1–7) is an endogenous ligand for the G protein-coupled receptor Mas. Proc Natl Acad Sci U S A. 2003;100(14):8258–8263.
    1. Santos RA, Castro CH, Gava E, et al. Impairment of in vitro and in vivo heart function in angiotensin-(1–7) receptor MAS knockout mice. Hypertension. 2006;47(5):996–1002.
    1. Castro CH, Santos RA, Ferreira AJ, Bader M, Alenina N, Almeida AP. Evidence for a functional interaction of the angiotensin-(1–7) receptor Mas with AT1 and AT2 receptors in the mouse heart. Hypertension. 2005;46(4):937–942.
    1. Dias-Peixoto MF, Santos RA, Gomes ER, et al. Molecular mechanisms involved in the angiotensin-(1–7)/Mas signaling pathway in cardiomyocytes. Hypertension. 2008;52(3):542–548.
    1. Gallagher PE, Ferrario CM, Tallant EA. MAP Kinase/phosphatase pathway mediates the regulation of ACE2 by angiotensin peptides. Am J Physiol Cell Physiol. 2008;295(5):C1169–C1174.
    1. Sampaio WO, Henrique de Castro C, Santos RA, Schiffrin EL, Touyz RM. Angiotensin-(1–7) counterregulates angiotensin II signaling in human endothelial cells. Hypertension. 2007;50(6):1093–1098.
    1. Crackower MA, Sarao R, Oudit GY, et al. Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature. 2002;417(6891):822–828.
    1. Ferrario CM. Angiotensin-converting enzyme 2 and angiotensin-(1–7): an evolving story in cardiovascular regulation. Hypertension. 2006;47(3):515–521.
    1. Lu H, Rateri DL, Feldman DL, et al. Renin inhibition reduces hypercholesterolemia-induced atherosclerosis in mice. J Clin Invest. 2008;118(3):984–993.
    1. Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345(12):861–869.
    1. Cohn JN, Tognoni G. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001;345(23):1667–1675.
    1. Dickstein K, Kjekshus J. Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Optimal Trial in Myocardial Infarction with Angiotensin II Antagonist Losartan. Lancet. 2002;360(9335):752–760.
    1. Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345(12):851–860.
    1. Parving HH, Lehnert H, Brochner-Mortensen J, Gomis R, Andersen S, Arner P. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med. 2001;345(12):870–878.
    1. Pfeffer MA, McMurray JJ, Velazquez EJ, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med. 2003;349(20):1893–1906.
    1. Pfeffer MA, Swedberg K, Granger CB, et al. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet. 2003;362(9386):759–766.
    1. The_ONTARGET_Investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358:1547–1559.
    1. Strawn WB, Ferrario CM, Tallant EA.Angiotensin-(1–7) reduces smooth muscle growth after vascular injury Hypertension 199933(1 Pt 2):207–211.
    1. Ishiyama Y, Gallagher PE, Averill DB, Tallant EA, Brosnihan KB, Ferrario CM. Upregulation of angiotensin-converting enzyme 2 after myocardial infarction by blockade of angiotensin II receptors. Hypertension. 2004;43(5):970–976.
    1. Ferrario CM, Trask AJ, Jessup JA. Advances in biochemical and functional roles of angiotensin-converting enzyme 2 and angiotensin-(1–7) in regulation of cardiovascular function. Am J Physiol Heart Circ Physiol. 2005;289(6):H2281–H2290.
    1. Igase M, Strawn WB, Gallagher PE, Geary RL, Ferrario CM. Angiotensin II AT1 receptors regulate ACE2 and angiotensin-(1–7) expression in the aorta of spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol. 2005;289(3):H1013–H1019.
    1. Tallant EA, Ferrario CM, Gallagher PE. Angiotensin-(1–7) inhibits growth of cardiac myocytes through activation of the mas receptor. Am J Physiol Heart Circ Physiol. 2005;289(4):H1560–H1566.
    1. Yokoyama H, Averill DB, Brosnihan KB, Smith RD, Schiffrin EL, Ferrario CM. Role of blood pressure reduction in prevention of cardiac and vascular hypertrophy. Am J Hypertens. 2005;18(7):922–929.
    1. Agata J, Ura N, Yoshida H, et al. Olmesartan is an angiotensin II receptor blocker with an inhibitory effect on angiotensin-converting enzyme. Hypertens Res. 2006;29(11):865–874.
    1. Trask AJ, Averill DB, Ganten D, Chappell MC, Ferrario CM. Primary role of angiotensin-converting enzyme-2 in cardiac production of angiotensin-(1–7) in transgenic Ren-2 hypertensive rats. Am J Physiol Heart Circ Physiol. 2007;292(6):H3019–H3024.
    1. Trask AJ, Ferrario CM. Angiotensin-(1–7): pharmacology and new perspectives in cardiovascular treatments. Cardiovasc Drug Rev. 2007;25(2):162–174.
    1. Gallagher PE, Ferrario CM, Tallant EA. Regulation of ACE2 in cardiac myocytes and fibroblasts. Am J Physiol Heart Circ Physiol. 2008;295(6):H2373–H2379.
    1. Igase M, Kohara K, Nagai T, Miki T, Ferrario CM. Increased expression of angiotensin converting enzyme 2 in conjunction with reduction of neointima by angiotensin II type 1 receptor blockade. Hypertens Res. 2008;31(3):553–559.
    1. Fliser D, Buchholz K, Haller H. Antiinflammatory effects of angiotensin II subtype 1 receptor blockade in hypertensive patients with microinflammation. Circulation. 2004;110(9):1103–1107.
    1. Bahlmann FH, de Groot K, Mueller O, Hertel B, Haller H, Fliser D. Stimulation of endothelial progenitor cells: a new putative therapeutic effect of angiotensin II receptor antagonists. Hypertension. 2005;45(4):526–529.
    1. Stumpe K, Agabiti-Rosei E, Zielinski T, et al. Carotid intima-media thickness and plaque volume changes following 2-year angiotensin II-receptor blockade. The multicentre olmesartan atherosclerosis regresssion evaluation (MORE) study. Ther Adv Cardiovasc Dis. 2007;1(2):97–106.
    1. Naya M, Tsukamoto T, Morita K, et al. Olmesartan, but not amlodipine, improves endothelium-dependent coronary dilation in hypertensive patients. J Am Coll Cardiol. 2007;50(12):1144–1149.
    1. Smith R, Yokoyama H, Averill DB, Schiffrin EL, Ferrario CM. Reversal of vascular hypertrophy in hypertensive patients through blockade of angiotensin II receptors. JASH. 2008;2(3):165–172.
    1. Smith RD, Yokoyama H, Averill DB, et al. The protective effects of angiotensin II blockade with olmesartan medoxomil on resistance vessel remodeling (The VIOS study): rationale and baseline characteristics. Am J Cardiovasc Drugs. 2006;6(5):335–342.
    1. Yamamoto E, Dong YF, Kataoka K, et al. Olmesartan prevents cardiovascular injury and hepatic steatosis in obesity and diabetes, accompanied by apoptosis signal regulating kinase-1 inhibition. Hypertension. 2008;52(3):573–580.
    1. Izumiya Y, Kim S, Izumi Y, et al. Apoptosis signal-regulating kinase 1 plays a pivotal role in angiotensin II-induced cardiac hypertrophy and remodeling. Circ Res. 2003;93(9):874–883.
    1. Porteri E, Rodella L, Rizzoni D, et al. Effects of olmesartan and enalapril at low or high doses on cardiac, renal and vascular interstitial matrix in spontaneously hypertensive rats. Blood Press. 2005;14(3):184–192.
    1. Yoshida J, Yamamoto K, Mano T, et al. AT1 receptor blocker added to ACE inhibitor provides benefits at advanced stage of hypertensive diastolic heart failure. Hypertension. 2004;43(3):686–691.
    1. Miyazaki M, Takai S. Anti-atherosclerotic efficacy of olmesartan. J Hum Hypertens. 2002;16(Suppl 2):S7–S12.
    1. Takai S, Jin D, Sakaguchi M, Muramatsu M, Miyazaki M. The regressive effect of an angiotensin II receptor blocker on formed fatty streaks in monkeys fed a high-cholesterol diet. J Hypertens. 2005;23(10):1879–1886.
    1. Kato M, Sada T, Mizuno M, Kitayama K, Inaba T, Koike H. Effect of combined treatment with an angiotensin II receptor antagonist and an HMG-CoA reductase inhibitor on atherosclerosis in genetically hyperlipidemic rabbits. J Cardiovasc Pharmacol. 2005;46(4):556–562.
    1. van der Hoorn JW, Kleemann R, Havekes LM, Kooistra T, Princen HM, Jukema JW. Olmesartan and pravastatin additively reduce development of atherosclerosis in APOE*3Leiden transgenic mice. J Hypertens. 2007;25(12):2454–2462.
    1. Yamamoto E, Yamashita T, Tanaka T, et al. Pravastatin enhances beneficial effects of olmesartan on vascular injury of salt-sensitive hypertensive rats, via pleiotropic effects. Arterioscler Thromb Vasc Biol. 2007;27(3):556–563.
    1. Tsuda M, Iwai M, Li JM, et al. Inhibitory effects of AT1 receptor blocker, olmesartan, and estrogen on atherosclerosis via anti-oxidative stress. Hypertension. 2005;45(4):545–551.
    1. Kato M, Sada T, Chuma H, et al. Severity of hyperlipidemia does not affect antiatherosclerotic effect of an angiotensin II receptor antagonist in apolipoprotein E-deficient mice. J Cardiovasc Pharmacol. 2006;47(6):764–769.
    1. Koga K, Yamagishi S, Takeuchi M, et al. CS-886, a new angiotensin II type 1 receptor antagonist, ameliorates glomerular anionic site loss and prevents progression of diabetic nephropathy in Otsuka Long-Evans Tokushima fatty rats. Mol Med. 2002;8(10):591–599.
    1. Kobori H, Ozawa Y, Suzaki Y, Nishiyama A. Enhanced intrarenal angiotensinogen contributes to early renal injury in spontaneously hypertensive rats. J Am Soc Nephrol. 2005;16(7):2073–2080.
    1. Nangaku M, Miyata T, Sada T, et al. Anti-hypertensive agents inhibit in vivo the formation of advanced glycation end products and improve renal damage in a type 2 diabetic nephropathy rat model. J Am Soc Nephrol. 2003;14(5):1212–1222.
    1. Izuhara Y, Nangaku M, Inagi R, et al. Renoprotective properties of angiotensin receptor blockers beyond blood pressure lowering. J Am Soc Nephrol. 2005;16(12):3631–3641.
    1. Nakamura H, Inoue T, Arakawa N, et al. Pharmacological and pharmacokinetic study of olmesartan medoxomil in animal diabetic retinopathy models. Eur J Pharmacol. 2005;512:2–3. 239–246.
    1. Jinno T, Iwai M, Li Z, et al. Calcium channel blocker azelnidipine enhances vascular protective effects of AT1 receptor blocker olmesartan. Hypertension. 2004;43(2):263–269.
    1. Liu HW, Iwai M, Takeda-Matsubara Y, et al. Effect of estrogen and AT1 receptor blocker on neointima formation. Hypertension. 2002;40(4):451–457.
    1. Min LJ, Mogi M, Li JM, Iwanami J, Iwai M, Horiuchi M. Aldosterone and angiotensin II synergistically induce mitogenic response in vascular smooth muscle cells. Circ Res. 2005;97(5):434–442.
    1. Mukai Y, Shimokawa H, Higashi M, et al. Inhibition of renin-angiotensin system ameliorates endothelial dysfunction associated with aging in rats. Arterioscler Thromb Vasc Biol. 2002;22(9):1445–1450.
    1. Ferrario CM. The role of angiotensin antagonism in stroke prevention in patients with hypertension: focus on losartan. Curr Med Res Opin. 2004;20(11):1797–1804.
    1. Fabia MJ, Abdilla N, Oltra R, Fernandez C, Redon J. Antihypertensive activity of angiotensin II AT1 receptor antagonists: a systematic review of studies with 24 h ambulatory blood pressure monitoring. J Hypertens. 2007;25(7):1327–1336.
    1. Koike H, Sada T, Mizuno M. In vitro and in vivo pharmacology of olmesartan medoxomil, an angiotensin II type AT1 receptor antagonist. J Hypertens Suppl. 2001;19(1):S3–S14.
    1. Yanagisawa H, Amemiya Y, Kanazaki T, et al. Nonpeptide angiotensin II receptor antagonists: synthesis, biological activities, and structure-activity relationships of imidazole-5-carboxylic acids bearing alkyl, alkenyl, and hydroxyalkyl substituents at the 4-position and their related compounds. J Med Chem. 1996;39(1):323–338.
    1. Le MT, Pugsley MK, Vauquelin G, Van Liefde I. Molecular characterisation of the interactions between olmesartan and telmisartan and the human angiotensin II AT1 receptor. Br J Pharmacol. 2007;151(7):952–962.
    1. Ichikawa S, Takayama Y. Long-term effects of olmesartan, an Ang II receptor antagonist, on blood pressure and the renin-angiotensin-aldosterone system in hypertensive patients. Hypertens Res. 2001;24(6):641–646.
    1. Schindler C, Brosnihan KB, Ferrario CM, et al. Comparison of inhibitory effects of irbesartan and atorvastatin treatment on the renin angiotensin system (RAS) in veins: a randomized double-blind crossover trial in healthy subjects. J Clin Pharmacol. 2007;47(1):112–120.
    1. Iyer SN, Averill DB, Chappell MC, Yamada K, Allred AJ, Ferrario CM. Contribution of angiotensin-(1–7) to blood pressure regulation in salt-depleted hypertensive rats. Hypertension. 2000;36(3):417–422.
    1. Moriguchi A, Tallant EA, Matsumura K, et al. Opposing actions of angiotensin-(1–7) and angiotensin II in the brain of transgenic hypertensive rats. Hypertension. 1995;25(6):1260–1265.
    1. Campagnole-Santos MJ, Heringer SB, Batista EN, Khosla MC, Santos RA.Differential baroreceptor reflex modulation by centrally infused angiotensin peptides Am J Physiol 1992263(1 Pt 2):R89–R94.
    1. Grobe JL, Mecca AP, Lingis M, et al. Prevention of angiotensin II-induced cardiac remodeling by angiotensin-(1–7) Am J Physiol Heart Circ Physiol. 2007;292(2):H736–H742.
    1. Ferreira AJ, Santos RA, Almeida AP.Angiotensin-(1–7): cardioprotective effect in myocardial ischemia/reperfusion Hypertension 200138(3 Pt 2): 665–668.
    1. Ferreira AJ, Santos RA, Almeida AP. Angiotensin-(1–7) improves the post-ischemic function in isolated perfused rat hearts. Braz J Med Biol Res. 2002;35(9):1083–1090.
    1. DelliPizzi AM, Hilchey SD, Bell-Quilley CP. Natriuretic action of angiotensin(1–7) Br J Pharmacol. 1994;111(1):1–3.
    1. Heller J, Kramer HJ, Maly J, Cervenka L, Horacek V. Effect of intrarenal infusion of angiotensin-(1–7) in the dog. Kidney Blood Press Res. 2000;23(2):89–94.
    1. Vallon V, Heyne N, Richter K, Khosla MC, Fechter K. [7-D-ALA]-angiotensin 1–7 blocks renal actions of angiotensin 1–7 in the anesthetized rat. J Cardiovasc Pharmacol. 1998;32(1):164–167.
    1. Loot AE, Roks AJ, Henning RH, et al. Angiotensin-(1–7) attenuates the development of heart failure after myocardial infarction in rats. Circulation. 2002;105(13):1548–1550.
    1. Ferrario CM, Martell N, Yunis C, et al. Characterization of angiotensin-(1–7) in the urine of normal and essential hypertensive subjects. Am J Hypertens. 1998;11(2):137–146.
    1. Luque M, Martin P, Martell N, Fernandez C, Brosnihan KB, Ferrario CM. Effects of captopril related to increased levels of prostacyclin and angiotensin-(1–7) in essential hypertension. J Hypertens. 1996;14(6):799–805.
    1. Ferrario CM, Smith RD, Brosnihan B, et al. Effects of omapatrilat on the renin-angiotensin system in salt-sensitive hypertension. Am J Hypertens. 2002;15(6):557–564.
    1. Schmeider RE, Hilgers KF, Schlaich MP. Renin-angiotensin system and cardiovascular risk. Lancet. 2007;369:1208–1219.

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