Practical Considerations of the Pharmacology of Angiotensin Receptor Blockers

Abstract

A review of the drug class of angiotensin receptor blockers (ARBs) as well as the ARBs currently available by prescription in the United States is presented. The importance of angiotensin II production by non-angiotensin-converting enzyme (non-ACE) pathways, particularly human chymase, is discussed. Emphasis is placed on the mechanism of action of ARBs and the different binding kinetics of these agents. Although all ARBs, as a group, block the AT1 receptor, they may differ in the pharmacological characteristics of their binding and be classified as either surmountable or insurmountable antagonists. Mechanisms of surmountable and insurmountable antagonism as well as possible benefits of these blocking characteristics are discussed in relation to the various ARBs. The cardiovascular effects of activation of the two main subtypes of angiotensin receptors (AT1 and AT2) are presented. In addition to their treatment of hypertension, ACE inhibitors are recognized as being effective in the management of heart failure, left ventricular hypertrophy, recurrent myocardial infarctions, and renal disease. ARBs are currently indicated only for the treatment of hypertension; however, in vitro and in vivo pharmacological studies as well as preliminary clinical data suggest that ARBs, like ACE inhibitors, may also provide effective protection against end-organ damage in these conditions.

Effect of losartan and spironolactone on left ventricular mass and heart sympathetic activity in prehypertensive obese subjects: a 16-week randomized trial

“…31 However, we did not find spironolactone effects on heart sympathetic activity or LVM after 16 weeks of treatment. These results are in contrast with McConnaughey et al, 11 because spironolactone treatment for patients with heart failure reduced circulating levels of procollagen type III N-terminal aminopeptide, indicating antifibrotic effect. Thus, it seems that blocking aldosterone receptors is not enough to modify LVM in prehypertensive obese subjects, or that more time is needed to observe spironolactone effects on LVM and heart sympathetic activity.…”

“…Ang II induces cardiac and vascular cell hypertrophy directly by activating the angiotensin II type 1(AT1) receptor and indirectly by stimulating release of several growth factors and cytokines. 11 In contrast to ACE inhibitors, which lower the levels of Ang II, Ang II antagonists increase concentrations of the peptide via inhibition of the negative feedback mechanisms through blockade of the AT1-receptor.…”

“…10 Of importance, Ang II induces cardiac and vascular cell hypertrophy and hyperplasia directly by activating the angiotensin II type 1(AT1) receptor and indirectly by stimulating release of several growth factors and cytokines. 11 Thus, it seems that either: ACE, AT1 receptor, or aldosterone blockers could have a beneficial effect on haemodynamic and anatomical changes produced by obesity.…”

Correlation of Hypotension and Hypertension With Vata, Pita and Kapha as Basic Constituents

“…Angiotensin II causes vasoconstriction as well as release of aldosterone from adrenal glands 35,36 . Obesity is a risk factor for hypertension because of activation of the renin-angiotensin system (RAS) in adipose tissue 32,37 , and also linked reninangiotensin system with insulin resistance 38 .…”

Pharmacokinetics and pharmacodynamics (PK/PD) of irbesartan in Beagle dogs after oral administration at two dose rates

“…Beside AT1 receptors, angiotensin II type 2 receptors (AT2) have also been described in several organs and Correspondence to: M. Giorgi, e-mail: mgiorgi@vet.unipi.it, tel. : +39 502 210 154 tissues (Ruilope 1997, McConnaughey et al 1999). However, Irb shows a higher affinity (more than 8500 times) for AT1 receptors versus AT2 receptors and does not show any agonistic activity on AT2 receptors (Ruilope 1997).…”