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Renal effects of ACE inhibitors in hypertension

Johannes FE Mann, MD
Karl F Hilgers, MD
Section Editors
George L Bakris, MD
Norman M Kaplan, MD
Deputy Editor
John P Forman, MD, MSc


The effect of angiotensin-converting enzyme (ACE) inhibitors on renal function in the hypertensive patient is related both to the glomerular actions of angiotensin II and to the mechanism of autoregulation of the glomerular filtration rate (GFR) [1]. Angiotensin II constricts both the afferent and efferent arterioles, but preferentially increases efferent resistance [2]. At least three factors may contribute to this response:

The efferent arteriole has a smaller diameter in the basal state; as a result, further constriction at this site will produce a greater increase in resistance than at the afferent arteriole [2]

Angiotensin II stimulates the release of the vasodilator nitric oxide from the afferent arteriole, thereby minimizing constriction at this site [3]

Angiotensin II minimizes vasoconstriction at the afferent arteriole via the stimulation of angiotensin II type 2 receptors, which results in vasodilation through a cytochrome P450 dependent pathway [4-6]

The net effect of the more prominent increase in efferent tone is that the intraglomerular pressure is stable or increased, thereby tending to maintain or even raise the GFR. In addition to these arteriolar actions, angiotensin II constricts the mesangial cells, an effect that tends to lower the GFR by decreasing the surface area available for filtration.

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Literature review current through: Nov 2017. | This topic last updated: May 16, 2017.
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  1. Braam B, Koomans HA. Renal responses to antagonism of the renin-angiotensin system. Curr Opin Nephrol Hypertens 1996; 5:89.
  2. Denton KM, Fennessy PA, Alcorn D, Anderson WP. Morphometric analysis of the actions of angiotensin II on renal arterioles and glomeruli. Am J Physiol 1992; 262:F367.
  3. Ito S, Arima S, Ren YL, et al. Endothelium-derived relaxing factor/nitric oxide modulates angiotensin II action in the isolated microperfused rabbit afferent but not efferent arteriole. J Clin Invest 1993; 91:2012.
  4. Arima S, Endo Y, Yaoita H, et al. Possible role of P-450 metabolite of arachidonic acid in vasodilator mechanism of angiotensin II type 2 receptor in the isolated microperfused rabbit afferent arteriole. J Clin Invest 1997; 100:2816.
  5. Arima S. Role of angiotensin II and endogenous vasodilators in the control of glomerular hemodynamics. Clin Exp Nephrol 2003; 7:172.
  6. Kohagura K, Endo Y, Ito O, et al. Endogenous nitric oxide and epoxyeicosatrienoic acids modulate angiotensin II-induced constriction in the rabbit afferent arteriole. Acta Physiol Scand 2000; 168:107.
  7. Hall JE, Guyton AC, Jackson TE, et al. Control of glomerular filtration rate by renin-angiotensin system. Am J Physiol 1977; 233:F366.
  8. Hollenberg NK, Swartz SL, Passan DR, Williams GH. Increased glomerular filtration rate after converting-enzyme inhibition in essential hypertension. N Engl J Med 1979; 301:9.
  9. Reams GP, Bauer JH. Effect of lisinopril monotherapy on renal hemodynamics. Am J Kidney Dis 1988; 11:499.
  10. Toto RD, Mitchell HC, Lee HC, et al. Reversible renal insufficiency due to angiotensin converting enzyme inhibitors in hypertensive nephrosclerosis. Ann Intern Med 1991; 115:513.
  11. Agodoa LY, Appel L, Bakris GL, et al. Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial. JAMA 2001; 285:2719.
  12. Kidney Disease Outcomes Quality Initiative (K/DOQI). K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis 2004; 43:S1.
  13. Himmelmann A, Hansson L, Hansson BG, et al. ACE inhibition preserves renal function better than beta-blockade in the treatment of essential hypertension. Blood Press 1995; 4:85.
  14. Hricik DE. Captopril-induced renal insufficiency and the role of sodium balance. Ann Intern Med 1985; 103:222.
  15. van de Ven PJ, Beutler JJ, Kaatee R, et al. Angiotensin converting enzyme inhibitor-induced renal dysfunction in atherosclerotic renovascular disease. Kidney Int 1998; 53:986.
  16. Jaichenko J, Fudin R, Shostak A, Gotloib L. Use of angiotensin-converting enzyme inhibitors in patients with diabetic and nondiabetic chronic renal diseases: a need for reassessment. Nephron 1998; 80:367.
  17. Mimran A, Ribstein J, DuCailar G. Converting enzyme inhibitors and renal function in essential and renovascular hypertension. Am J Hypertens 1991; 4:7S.
  18. Franklin SS, Smith RD. Comparison of effects of enalapril plus hydrochlorothiazide versus standard triple therapy on renal function in renovascular hypertension. Am J Med 1985; 79:14.
  19. Izzo JL Jr, Weir MR. Angiotensin-converting enzyme inhibitors. J Clin Hypertens (Greenwich) 2011; 13:667.
  20. Chrysochou C, Foley RN, Young JF, et al. Dispelling the myth: the use of renin-angiotensin blockade in atheromatous renovascular disease. Nephrol Dial Transplant 2012; 27:1403.
  21. Losito A, Errico R, Santirosi P, et al. Long-term follow-up of atherosclerotic renovascular disease. Beneficial effect of ACE inhibition. Nephrol Dial Transplant 2005; 20:1604.
  22. Losito A, Gaburri M, Errico R, et al. Survival of patients with renovascular disease and ACE inhibition. Clin Nephrol 1999; 52:339.
  23. Miyamori I, Yasuhara S, Matsubara T, et al. Comparative effects of captopril and nifedipine on split renal function in renovascular hypertension. Am J Hypertens 1988; 1:359.
  24. Textor SC, Novick AC, Tarazi RC, et al. Critical perfusion pressure for renal function in patients with bilateral atherosclerotic renal vascular disease. Ann Intern Med 1985; 102:308.
  25. Devoy MA, Tomson CR, Edmunds ME, et al. Deterioration in renal function associated with angiotensin converting enzyme inhibitor therapy is not always reversible. J Intern Med 1992; 232:493.
  26. Hannedouche T, Godin M, Fries D, Fillastre JP. Acute renal thrombosis induced by angiotensin-converting enzyme inhibitors in patients with renovascular hypertension. Nephron 1991; 57:230.
  27. Wenting GJ, Tan-Tjiong HL, Derkx FH, et al. Splint renal function after captopril in unilateral renal artery stenosis. Br Med J (Clin Res Ed) 1984; 288:886.
  28. Jackson B, McGrath BP, Matthews PG, et al. Differential renal function during angiotensin converting enzyme inhibition in renovascular hypertension. Hypertension 1986; 8:650.
  29. Hricik DE, Dunn MJ. Angiotensin-converting enzyme inhibitor-induced renal failure: causes, consequences, and diagnostic uses. J Am Soc Nephrol 1990; 1:845.
  30. Onuigbo MA, Onuigbo NT. Use of ultrahigh RAAS blockade: implications for exacerbation of renal failure. Kidney Int 2006; 69:194.
  31. Ahmed AK, Kamath NS, El Kossi M, El Nahas AM. The impact of stopping inhibitors of the renin-angiotensin system in patients with advanced chronic kidney disease. Nephrol Dial Transplant 2010; 25:3977.