Journal of the American Society of Hypertension
Volume 1, Issue 6 , Pages 423-432 , November 2007

Telmisartan ramipril combination therapy reduces strokes and improves cardiac and renal protection in stroke prone spontaneously hypertensive rats

  • Ying Zhou, MD
    • ,
  • Fangmin Yu, PharmD
    • ,
  • Ada R. Ene, MD
    • ,
  • Daniel F. Catanzaro, PhD

      Affiliations

    • Corresponding Author InformationCorresponding author: Daniel F. Catanzaro, Weill Cornell Medical College, Division of Cardiovascular Pathophysiology, 1300 York Avenue, Box 118, New York, New York 10065. Tel: 212-746-6335.

Received 20 April 2007 ,Accepted 13 August 2007.

References 

  1. Rocha R, Chander PN, Zuckerman A, Stier CT. Role of aldosterone in renal vascular injury in stroke-prone hypertensive rats. Hypertension. 1999;33:232–237
  2. Stier CTJ, Chander P, Gutstein WH, Levine S, Itskovitz HD. Therapeutic benefit of captopril in salt-loaded stroke-prone spontaneously hypertensive rats is independent of hypertensive effect. Am J Hypertens. 1991;4:680–687
  3. von Lutterotti N, Camargo MJF, Campbell WG, Mueller FB, Timmermans PBMWM, Sealey JE, et al. Angiotensin II receptor antagonist delays renal damage and stroke in salt-loaded Dahl salt-sensitive rats. J Hypertens. 1992;10:949–957
  4. Camargo MJ, von Lutterotti N, Campbell WG, Pecker MS, James GD, Timmermans PB, et al. Control of blood pressure and end-organ damage in maturing salt-loaded stroke-prone spontaneously hypertensive rats by oral angiotensin II receptor blockade. J Hypertens. 1993;11:31–40
  5. Barone F, Coatney R, Chandra S, Sarkar S, Nelson A, Contino L, et al. Eprosartan reduces cardiac hypertrophy, protects heart and kidney, and prevents early mortality in severely hypertensive stroke-prone rats. Cardiovasc Res. 2001;50:525–537
  6. SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension (Final results of the Systolic Hypertension in the Elderly Program). JAMA. 1991;265:3255–3264
  7. Biollaz J, Brunner HR, Gavras I, Waeber B, Gavras H. Antihypertensive therapy with MK 421: angiotensin II—renin relationships to evaluate efficacy of converting enzyme blockade. J Cardiovasc Pharmacol. 1982;4:966–972
  8. Hornig B, Kohler C, Drexler H. Role of bradykinin in mediating vascular effects of angiotensin-converting enzyme inhibitors in humans. Circulation. 1997;95:1115–1118
  9. Azizi M, Guyene TT, Chatellier G, Wargon M, Menard J. Additive effects of losartan and enalapril on blood pressure and plasma active renin. Hypertension. 1997;29:634–640
  10. Mogensen CE, Neldam S, Tikkanen I, Oren S, Viskoper R, Watts RW, et al. Randomized controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the CAndesartan and Lisinopril Microalbuminuria (CALM) Study. BMJ. 2000;321:1440–1444
  11. Ruilope L, Aldigier J, Ponticelli C, Oddou-Stock P, Botteri F, Mann J. Safety of the combination of valsartan and benazepril in patients with chronic renal disease (European Group for the Investigation of Valsartan in Chronic Renal Disease). J Hypertens. 2000;18:89–95
  12. Rossing K, Jacobsen P, Pietraszek L, Parving H. Renoprotective effects of adding angiotensin II receptor blocker to maximal recommended doses of ACE inhibitor in diabetic nephropathy: a randomized double-blind crossover trial. Diabetes Care. 2003;26:2268–2274
  13. Russo D, Minutolo R, Pisani A, Esposito R, Signoriello G, Andreucci M, et al. Coadministration of losartan and enalapril exerts additive antiproteinuric effect in IgA nephropathy. Am J Kidney Dis. 2001;38:18–25
  14. Nakao N, Yoshimura A, Morita H, Takada M, Kayano T, Ideura T. Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomized controlled trial. Lancet. 2003;361:117–124
  15. Ferrari P, Marti H, Pfister M, Frey F. Additive antiproteinuric effect of combined ACE inhibition and angiotensin II receptor blockade. J Hypertens. 2002;20:125–130
  16. Laverman GD, Navis G, Henning RH, de Jong PE, de Zeeuw D. Dual renin-angiotensin system blockade at optimal doses for proteinuria. Kidney Int. 2002;62:1020–1025
  17. Young JB, Dunlap ME, Pfeffer MA, Probstfield JL, Cohen-Solal A, Dietz R, et al. Mortality and morbidity reduction with candesartan in patients with chronic heart failure and left ventricular systolic dysfunction: results of the CHARM low-left ventricular ejection fraction trials. Circulation. 2004;110:2618–2626
  18. McMurray JJ, Ostergren J, Swedberg K, Granger CB, Held P, Michelson EL, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial. Lancet. 2003;362:767–771
  19. Anan F, Takahashi N, Ooie T, Yufu K, Hara M, Nakagawa M, et al. Effects of valsartan and perindopril combination therapy on left ventricular hypertrophy and aortic arterial stiffness in patients with essential hypertension. Eur J Clin Pharmacol. 2005;61:353–359
  20. Camargo MJF, von Lutterotti N, Campbell WG, Pecker MS, James GD, Timmermans PBMWM, et al. Control of blood pressure and end-organ damage in maturing salt-loaded stroke-prone spontaneously hypertensive rats by oral angiotensin II receptor blockade. J. Hypertens. 1993;11:31–40
  21. Richer-Giudicelli C, Domergue V, Gonzalez MF, Messadi E, Azizi M, Giudicelli JF, et al. Hemodynamic effects of dual blockade of the renin-angiotensin system in spontaneously hypertensive rats: influence of salt. J Hypertens. 2004;22:619–627
  22. Menard J, Campbell DJ, Azizi M, Gonzales MF. Synergistic effects of ACE inhibition and Ang II antagonism on blood pressure, cardiac weight, and renin in spontaneously hypertensive rats. Circulation. 1997;96:3072–3078
  23. Kim S, Zhan Y, Izumi Y, Iwao H. Cardiovascular effects of combination of perindopril, candesartan, and amlodipine in hypertensive rats. Hypertension. 2000;35:769–774
  24. Morgan T, Griffiths C, Delbridge L. Low doses of angiotensin converting enzyme inhibitors and angiotensin type 1 blockers have a synergistic effect but high doses are less than additive. Am J Hypertens. 2002;15:1003–1005
  25. Morgan T, Griffiths C, Delbridge L. Interaction of ACE inhibitors and AT(1)-receptor blockers on maximum blood pressure response in spontaneous hypertensive rats. J Renin Angiotensin Aldosterone Syst. 2002;3:16–18
  26. Naelten G, Liu KL, Chapuis B, Lo M. Persistent effects on blood pressure and renal function of perindopril alone or combined with losartan in Lyon hypertensive rats. Am J Hypertens. 2005;18:699–706
  27. Hu L, Sealey J, Chen R, Zhou Y, Merali C, Shi Y, et al. Nitric oxide synthase inhibition accelerates the pressor response to low-dose angiotensin II, exacerbates target organ damage, and induces renin escape. Am J Hypertens. 2004;17:395–403
  28. Griffin KA, Abu-Amarah I, Picken M, Bidani AK. Renoprotection by ACE inhibition or aldosterone blockade is blood pressure-dependent. Hypertension. 2003;41:201–206
  29. Culman J, von Heyer C, Piepenburg B, Rascher W, Unger T. Effects of systemic treatment with irbesartan and losartan on central responses to angiotensin II in conscious, normotensive rats. Eur J Pharmacol. 1999;367:255–265
  30. Gohlke P, Weiss S, Jansen A, Wienen W, Stangier J, Rascher W, et al. AT1 receptor antagonist telmisartan administered peripherally inhibits central responses to angiotensin II in conscious rats. J Pharmacol Exp Ther. 2001;298:62–70
  31. Liebetrau M, Burggraf D, Wunderlich N, Jager G, Linz W, Hamann GF. ACE inhibition reduces activity of the plasminogen/plasmin and MMP systems in the brain of spontaneous hypertensive stroke-prone rats. Neurosci Lett. 2005;376:205–209
  32. Gohlke P, Scholkens B, Henning R, Urbach H, Unger T. Inhibition of converting enzyme in brain tissue and cerebrospinal fluid of rats following chronic oral treatment with the converting enzyme inhibitors ramipril and Hoe 288. J Cardiovasc Pharmacol. 1989;14:S32–S36
  33. Stier CTJ, Benter IF, Ahmad S, Zuo HL, Selig N, Roethel S, et al. Enalapril prevents stroke and kidney dysfunction in salt-loaded stroke-prone spontaneously hypertensive rats. Hypertension. 1989;13:115–121
  34. Chung O, Unger T. Angiotensin II receptor blockade and end-organ protection. Am J Hypertens. 1999;12:S150–S156
  35. van den Eijnden MM, de Bruin RJ, de Wit E, Sluiter W, Deinum J, Reudelhuber TL, et al. Transendothelial transport of renin-angiotensin system components. J Hypertens. 2002;20:2029–2037
  36. Rose JM, Audus KL. AT1 receptors mediate angiotensin II uptake and transport by bovine brain microvessel endothelial cells in primary culture. J Cardiovasc Pharmacol. 1999;33:30–35
  37. Tschope C, Schultheiss HP, Walther T. Multiple interactions between the renin-angiotensin and the kallikrein-kinin systems: role of ACE inhibition and AT1 receptor blockade. J Cardiovasc Pharmacol. 2002;39:478–487
  38. Kurtz TW. New treatment strategies for patients with hypertension and insulin resistance. Am J Med. 2006;119:S24–S30

 This work was supported by a Grant from Boehringer Ingelheim Pharma GmbH & Co. KG.

 Conflict of interest: none.

PII: S1933-1711(07)00168-4

doi: 10.1016/j.jash.2007.08.002

Journal of the American Society of Hypertension
Volume 1, Issue 6 , Pages 423-432 , November 2007

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