Differences between angiotensin-converting enzyme inhibitors and receptor blockers
- Timothy W Smith, MD, PhD
Timothy W Smith, MD, PhD
- Associate Professor of Medicine
- Washington University School of Medicine
- James P Morgan, MD, PhD
James P Morgan, MD, PhD
- Professor of Medicine
- Tufts University School of Medicine
Angiotensin-converting enzyme (ACE) inhibitors are widely used in the treatment of hypertension. They have also been effective in a number of other disorders, prolonging survival in patients with heart failure, coronary heart disease, and acute myocardial infarction, and slowing the rate of progression in chronic renal failure, particularly diabetic nephropathy. One limiting side effect in a minority of patients is cough, a side effect that does not appear to occur with increased frequency with the angiotensin receptor blockers (ARBs), which are as effective as the ACE inhibitors in the treatment of hypertension . (See "Renin-angiotensin system inhibition in the treatment of hypertension".)
The evidence that there are clinically important differences between these two classes of drugs will be reviewed here. The major side effects of these drugs are discussed separately. (See "Major side effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers".)
MECHANISMS OF ACTION
Angiotensin II is an oligopeptide of eight amino acids, formed from its precursor, angiotensinogen by a series of two enzymatic cleavages. Angiotensinogen is released into the circulation by the liver. Renin, produced by the kidney, in response to glomerular hypoperfusion, catalyzes cleavage of angiotensinogen to angiotensin I, an inactive decapeptide. Angiotensin I is in turn cleaved by angiotensin-converting enzyme (ACE) to produce angiotensin II. Angiotensin II binds to its specific receptors and exert its effects in the brain, kidney, adrenal, vascular wall, and the heart.
There are two well-described subtypes of angiotensin II receptors, designated AT1 and AT2, both of which have a high affinity for angiotensin II [2,3]:
●The AT1 subtype mediates the vasoconstrictor effect of angiotensin II and is generally thought to mediate angiotensin II-induced growth in the left ventricle and the arterial wall .
- Matchar DB, McCrory DC, Orlando LA, et al. Systematic review: comparative effectiveness of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for treating essential hypertension. Ann Intern Med 2008; 148:16.
- Timmermans PB, Wong PC, Chiu AT, et al. Angiotensin II receptors and angiotensin II receptor antagonists. Pharmacol Rev 1993; 45:205.
- Griendling KK, Lassègue B, Alexander RW. Angiotensin receptors and their therapeutic implications. Annu Rev Pharmacol Toxicol 1996; 36:281.
- Goodfriend TL, Elliott ME, Catt KJ. Angiotensin receptors and their antagonists. N Engl J Med 1996; 334:1649.
- Tsutsumi K, Saavedra JM. Characterization and development of angiotensin II receptor subtypes (AT1 and AT2) in rat brain. Am J Physiol 1991; 261:R209.
- Grady EF, Sechi LA, Griffin CA, et al. Expression of AT2 receptors in the developing rat fetus. J Clin Invest 1991; 88:921.
- Stoll M, Steckelings UM, Paul M, et al. The angiotensin AT2-receptor mediates inhibition of cell proliferation in coronary endothelial cells. J Clin Invest 1995; 95:651.
- Hornig B, Kohler C, Drexler H. Role of bradykinin in mediating vascular effects of angiotensin-converting enzyme inhibitors in humans. Circulation 1997; 95:1115.
- Gainer JV, Morrow JD, Loveland A, et al. Effect of bradykinin-receptor blockade on the response to angiotensin-converting-enzyme inhibitor in normotensive and hypertensive subjects. N Engl J Med 1998; 339:1285.
- Tomiyama H, Kushiro T, Abeta H, et al. Kinins contribute to the improvement of insulin sensitivity during treatment with angiotensin converting enzyme inhibitor. Hypertension 1994; 23:450.
- Chandrasekharan UM, Sanker S, Glynias MJ, et al. Angiotensin II-forming activity in a reconstructed ancestral chymase. Science 1996; 271:502.
- Urata H, Boehm KD, Philip A, et al. Cellular localization and regional distribution of an angiotensin II-forming chymase in the heart. J Clin Invest 1993; 91:1269.
- Nishimura H, Hoffmann S, Baltatu O, et al. Angiotensin I converting enzyme and chymase in cardiovascular tissues. Kidney Int Suppl 1996; 55:S18.
- Ju H, Gros R, You X, et al. Conditional and targeted overexpression of vascular chymase causes hypertension in transgenic mice. Proc Natl Acad Sci U S A 2001; 98:7469.
- Esteras R, Perez-Gomez MV, Rodriguez-Osorio L, et al. Combination use of medicines from two classes of renin-angiotensin system blocking agents: risk of hyperkalemia, hypotension, and impaired renal function. Ther Adv Drug Saf 2015; 6:166.