The Role of Double Renin-Angiotensin System Blockade

Abstract

Blockade of the renin-angiotensin system (RAS) is now recognized as an effective means of lowering blood pressure (BP) and protecting hypertensive patients from end-organ damage. There are nowadays three pharmacologic approaches to blockade of the RAS: with angiotensin-converting enzyme (ACE) inhibitors, introduced in the 1970s, with angiotensin II (Ang II) AT1 receptor blockers (ARBs), introduced in the 199 0s, and with direct renin inhibitors, a new class whose first agent, aliskiren, was introduced in 2006. Clinical studies with the first two classes have shown that neither one achieves complete blockade of the RAS. With chronic use of ACE inhibitors, there is a gradual return of Ang II towards pretreatment levels because enzymes other than ACE (e.g., chymase and others) can cleave off two aminoacids from the decapeptide Ang I, even though there is no evidence of ???escape?? in terms of BP control. With ARBs there is a partial blockade of AT1 receptors of variable degree and duration, depending on the affinity of each agent for the receptor and of the duration of the blockade (surmountable or insurmountable).