The effect of amlodipine besylate, losartan potassium, olmesartan medoxomil, and other antihypertensives on central aortic blood pressure and biomarkers of vascular function

Abstract

Biomarkers are being increasingly used in the study of cardiovascular disease because they provide readily quantifiable surrogate endpoints and allow accurate assessment of the effects of therapy on particular pathological processes. However, in order to be useful, biomarkers must be relevant, predictable, accurate, and reproducible. There is compelling evidence from large-scale clinical trials that inhibitors of the renin-angiotensin system [angiotensin-converting enzyme inhibitors and angiotensin type II receptor blockers (ARBs)] and calcium channel blockers (CCBs) may have beneficial effects beyond blood pressure control in the treatment of hypertension. Biomarkers are expected to provide further insight into these beneficial effects and allow for quantitative assessment. This review summarizes the published clinical evidence on the effects of various antihypertensive drugs, particularly ARBs (e.g. losartan and olmesartan medoxomil) and CCBs (e.g. amlodipine), alone and in combination with other agents (e.g. hydrochlorothiazide), on central aortic pressure and the biomarkers high-sensitivity C-reactive protein (hsCRP), adiponectin, cystatin C, homeostasis model assessment of insulin resistance (HOMA-IR), procollagen, tumor necrosis factor-α, and interleukin-6. Of these biomarkers, the benefits of antihypertensive therapy on hsCRP, adiponectin, and HOMA-IR reflect a potential for quantifiable long-term vascular benefits.

Current topics in angiotensin II type 1 receptor research: Focus on inverse agonism, receptor dimerization and biased agonism

“…Human disease states, such as hypertension, coronary artery disease, cardiac hypertrophy, heart failure, arrhythmia, stroke, diabetic nephropathy, and ischemic heart and renal diseases are associated with overstimulation of AT1R [3–6]. These disease conditions can be treated with AT1R blocking drugs, known as ARBs.…”

Structure-Function Basis of Attenuated Inverse Agonism of Angiotensin II Type 1 Receptor Blockers for Active-State Angiotensin II Type 1 Receptor

“…The AT1R is the principal regulator of blood pressure and body-fluid homeostasis, and it plays vital roles in cardiovascular and renal pathophysiology. Overstimulation of AT1R is implicated in hypertension, coronary artery disease, cardiac hypertrophy, heart failure, arrhythmia, stroke, diabetic nephropathy, and ischemic heart and renal disease states, which can be greatly reduced by treatment with ARBs (Khan, 2011;Vijayaraghavan and Deedwania, 2011;Lee et al, 2012;Vejakama et al, 2012). The ARBs are nonpeptide receptor inhibitors with a common biphenyl-tetrazole scaffold, including the well known clinically used antihypertension drugs Losartan, Candesartan, Valsartan, Irbesartan, Telmisartan, Eprosartan, Olmesartan, and Azilsartan.…”

Effects of Nebivolol on Aortic Compliance in Patients With Diabetes and Maximal Renin Angiotensin System Blockade: The EFFORT Study

“…In other clinical trials, RAS blockers and calcium channel blockers had a more pronounced and favorable effect on central arterial pressure compared with β‐blockers. Atenolol, a nonvasodilatory β‐blocker, was the most commonly studied and did not appear to reduce CV outcomes …”

“…Atenolol, a nonvasodilatory b-blocker, was the most commonly studied and did not appear to reduce CV outcomes. 12,[22][23][24] Differences in heart rate reduction between b-blockers may have influenced the results between RAS blockers and other b-blockers. However, in our study, all PWV measurements were corrected for a heart rate of 75, regardless of heart rate change from baseline.…”