AT1-receptor blockers: differences that matter

Abstract

The available angiotensin II type 1 (AT 1 )-receptor blockers differ markedly in their pharmacological properties and clinical efficacy. Losartan shifts the dose-response curve for angiotensin II to the right without affecting the maximal response; this antagonism can be overcome by increasing concentrations of angiotensin II and thus losartan acts as a surmountable antagonist. By contrast, other agents suppress the maximal response to angiotensin II to varying extents; this can not be overcome by increasing angiotensin concentrations and hence these agents are insurmountable antagonists. Receptor binding studies have shown that candesartan has the highest affinity for the AT 1 -receptor, followed by irbesartan, valsartan and losartan, and that candesartan dissociates from the receptor more slowly than other antagonists. A meta-analysis using an E Max model has shown that differences in receptor binding activity are reflected in differences in maximal antihypertensive

Perindopril and candesartan comparative efficacy and safety in type II diabetic hypertensive patients

“…It confirms our previous report where we demonstrated that perindopril decreased PAI-1 compared to losartan, in hypertensive, type II diabetic patients. 6 Finally, as expected, 4,6 AER was decreased at the end of the study in both groups (À47.1 and À44.5%, respectively). Our patients started as normoalbuminuric and remained normoalbuminuric for all the phases of the study, probably because the glycaemic control was good and the antihypertensive therapy stopped the possible progression to microalbuminuria.…”

“…3 Metabolic abnormalities as insulin resistance, impairment lipid profile, and decreased fibrinolytic activity can be improved by ACE inhibitors. 2 ARBs have been shown to retard the progression of albuminuria and the development and progression of nephropathy, 4 but there are few data of the ARBs action on metabolic parameters, especially in comparison with ACE inhibitors, in diabetic subjects.…”

Telmisartan and Irbesartan Therapy in Type 2 Diabetic Patients Treated with Rosiglitazone: Effects on Insulin-Resistance, Leptin and Tumor Necrosis Factor-.ALPHA.

“…In cases of mildto-moderate hypertension, monotherapy controls BP in 40% to 50% of patients. This level of efficacy is similar to those of angiotensin-converting enzyme (ACE) inhibitors, diuretics, calcium antagonists and β -blocking agents ( 4 ). AT 1 receptor blockers are particularly indicated for patients with hypertension who are being treated with ACE inhibitors and have developed side effects, such as cough or angioedema ( 5 ).…”

Differing Anti-Proteinuric Action of Candesartan and Losartan in Chronic Renal Disease

“…Similarly, it has recently been demonstrated that the progression of renal injury in diabetic nephropathy is prevented by the inhibition of ANG II activity by ARBs (5,6,18). Although these observations clearly indicate the renal protective action of ARBs, there exists some heterogeneity in their antagonistic activity on AT1 receptors (7,9,19,20). Furthermore, it has been demonstrated ARBs, like ACE-Is, enhance the production of NO via AT1 receptor blockade (10,21).…”