Protective Effects of Angiotensin II Interruption: Evidence for Antiinflammatory Actions

Nigel J. Dagenais, B.Sc.(Pharm.); Fakhreddin Jamali, Ph.D.

Disclosures

Pharmacotherapy. 2005;25(9):1213-1229. 

In This Article

Abstract and Introduction

Angiotensin II, the major effector molecule produced from the renin-angiotensin-aldosterone axis, is a vasoconstrictor contributing to hypertension. Evidence indicates, however, that angiotensin II also is a potent proinflammatory mediator with growth and remodeling effects. In vitro and in vivo studies have shown that angiotensin II blockade significantly reduces concentrations of proinflammatory mediators and oxidative stress products in numerous inflammatory models. Interruption of angiotensin II activity with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers has been beneficial for patients with inflammatory diseases. Much of this benefit occurs independent of the antihypertensive effect of angiotensin II interruption, suggesting a distinctive protective mechanism. Angiotensin II receptor blockers may represent a novel class of antiinflammatory drugs with indications far beyond cardiovascular diseases.

All drugs are developed with a certain indication in mind, but widespread use can often expand beyond the initial indication. For example, acetylsalicylic acid was originally marketed as an analgesic and antipyretic agent in the late 19th century.[1] However, documented antiplatelet activity of aspirin many years later expanded its use as a valuable agent for preventing heart attacks and strokes.[2] Similar off-label indications may be expanded to angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), which were originally developed for treatment of hypertension by blocking the vasoconstrictive effect of angiotensin II. Recent human trials have shown that angiotensin II interruption has benefit in cardiovascular disease, diabetes mellitus, and heart failure, often independent of the antihypertensive effect. In vitro and in vivo data suggest that this special benefit may be due to a novel antiinflammatory effect, and this is supported by evidence that angiotensin II is a proinflammatory mediator.

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