Background: Plasma aldosterone escape is found during long-term angiotensin-converting enzyme inhibitor therapy. Evidence for aldosterone production in cardiovascular tissues raised the question of whether or not aldosterone escape occurs in these tissues. Method: Spontaneously hypertensive rats were treated with enalapril (20 mg/kg/day) and losartan (50 mg/kg/day) for 20 weeks; untreated spontaneously hypertensive and Wistar rats were used as positive and normal controls, respectively. Ex vivo mesenteric artery and heart perfusion, high-performance liquid chromatography, and radioimmunoassay for aldosterone were performed. Results: The results showed that enalapril failed to significantly inhibit aldosterone production in mesenteric artery, myocardium and plasma. Losartan significantly inhibited aldosterone production to that of Wistar rats in the mesenteric artery, myocardium and plasma. Conclusion: This study provides the first evidence that long-term angiotensin-converting enzyme inhibition therapy induces aldosterone escape in hypertensive cardiovascular tissues, and angiotensin II subtype 1 receptor antagonist does not induce aldosterone escape in mesenteric artery, myocardium and plasma of spontaneously hypertensive rats.

1.
Struthers AD: Aldosterone escape during angiotensin-converting enzyme inhibitor therapy in chronic heart failure. J Card Fail 1996;2:47–54.
2.
Borghi C, Boschi S, Ambrosioni E, Melandri G, Branzi A, Magnani B: Evidence of a partial escape of renin-angiotensin-aldosterone blockade in patients with acute myocardial infarction treated with ACE inhibitors. J Clin Pharmacol 1993;33:40–45.
3.
Ol’binskaia LI, Golubev SA, Bol’shakova TD, Anastas’ina GV, Buniatian AF, Nosova AA: The anti-hypertensive activity of benazepril in the long-term treatment of hypertension patients and its effect on adrenal cortical function. Ter Arkh 1995;67:56–58.
4.
Struthers AD: Why does spironolactone improve mortality over and above an ACE inhibitor in chronic heart failure? Br J Clin Pharmacol 1999;47:479–482.
5.
Konstam MA, Patten RD, Thomas I, Ramahi T, La Bresh K, Goldman S, Lewis W, Gradman A, Self KS, Bittner V, Rand W, Kinan D, Smith JJ, Ford T, Segal R, Udelson JE: Effects of losartan and captopril on left ventricular volumes in elderly patients with heart failure: Results of the ELITE ventricular function sub-study. Am Heart J 2000;139:1081–1087.
6.
Goldberg MR, Bradstreet TE, McWilliams EJ, Tanaka WK, Lipert S, Bjornsson TD, Waldman SA, Osborne B, Pivadori L, Lewis G: Biochemical effects of losartan, a nonpeptide angiotensin II receptor antagonist, on the renin-angiotensin-aldosterone system in hypertensive patients. Hypertension 1995;25:37–46.
7.
Smith MC, Barrows S, Meibohm A, Shahinfar S, Simpson RL, Weigel K, Dunn MJ: The effects of angiotensin II receptor blockade with losartan on systemic blood pressure and renal and extra prostaglandin synthesis in women with essential hypertension. Am J Hypertens 1995;8:1177–1183.
8.
Takeda R, Takeda Y, Hatakeyama H, Iki K, Miyamori I, Wu P, Yamamoto H, Blair IA: Aldosterone biosynthesis and action in vascular cells. Steroids 1995;60:120–124.
9.
Silvestre JS, Robert V, Heymes C, Aupetit-Faisant B, Mouas C, Moalic JM, Swynghedauw B, Delcayre C: Myocardial production of aldosterone and corticosterone in the rat physiological regulation. J Biol Chem 1998;273:4883–4891.
10.
Wu P, Zhang Y, Liu Y, Wang X, Guo Z, Zhang Y, Liang X, Lai W: Effects of cholic acid on blood pressure and production of vascular aldosterone and corticosterone. Steroids 1999;64:291–295.
11.
Miyamori I, Takeda Y, Yasuhara S, Ikeda M, Takeda R: Participation of vascular prostacyclin of experimental glucocorticoid hypertension in rats. Clin Exp Hypertens 1985;A7:513–524.
12.
Curtis MJ, Macleod BA, Tabrizchi R, Walker MJ: An improved perfusion apparatus for small animal hearts. J Pharmacol Methods 1986;15:87–94.
13.
Oaks MK, Raff H: Differentiation of the expression of aldosterone synthase and 11β-hydroxylase mRNA in the rat adrenal cortex by reverse transcriptase polymerase chain reaction. J Steroid Biochem Mol Biol 1995;54:193–199.
14.
Junji N, Xi C, Hasna J: cAMP induces up-regulation of ETA receptor mRNA and increases responsiveness to endothelin-1 of rat aortic smooth muscle cells in primary culture. Biochem Biophys Res Commun 1992;188:719–726.
15.
Di Pasquale P, Bucca V, Scalzo S, Paterna S: Safety, tolerability, and neurohormonal changes of the combination captopril plus losartan in the early postinfarction period: A pilot study. Cardiovasc Drugs Ther 1998;12:211–216.
16.
Ilett KF, Lockett MF: A renal active substance from heart muscle and from blood. J Physiol 1968;196:101–109.
17.
Wu P, Guo Z, Zhang Y, Liu Y, Liang X, Zhang R, Lai W, Takeda Y, Isamu M, Takeda R: Aldosterone overproduction and CYP11B2 mRNA overexpression in vessels of spontaneously hypertensive rats. Horm Res 1998;50:28–31.
18.
Urata H, Strobel F, Ganten D: Widespread tissue distribution of human chymase. J Hypertens 1994;12(suppl):S17–S22.
19.
Dina R, Jafari M: Angiotensin II-receptor antagonists: An overview. Am J Health Syst Pharmacol 2000;57:1231–1241.
20.
Hernandez-Hernandez R, Velasco M, Armas-Hernandez MJ, Armas-Padilla MC: Angiotensin II receptor antagonists in arterial hypertension. J Hum Hypertens 2000;14(suppl 1):S69–S72.
21.
Farsang C, Garcia-Puig J, Niegowska J, Baiz AQ, Vrijens F, Bortman G: The efficacy and tolerability of losartan versus atenolol in patients with isolated systolic hypertension. Losartan ISH Investigators Group. J Hypertens 2000;18:795–801.
22.
Silvestre JS, Heymes C, Oubenaissa A, Robert V, Aupetit-Faisant B, Carayon A, Swynghedauw B, Delcayre C: Activation of cardiac aldosterone production in rat myocardial infarction: Effect of angiotensin II receptor blockade and role in cardiac fibrosis. Circulation 1999;99:2694–2701.
23.
Van Zwieten PA: The role of angiotensin II receptors and their antagonists in hypertension. Ann Ital Med Int 2000;15:85–91.
24.
Mantero F, Lucarelli G: Aldosterone antagonists in hypertension and heart failure. Ann Endocrinol (Paris) 2000;61:52–60.
25.
Funck RC, Wilke A, Rupp H, Brilla CG: Regulation and role of myocardial collagen matrix remodeling in hypertensive heart disease. Adv Exp Med Biol 1997;432:35–44.
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