Metabolic actions of angiotensin receptor antagonists: PPAR-γ agonist actions or a class effect?

Abstract

Accumulating basic and clinical data support the hypothesis that angiotensin receptor blockers have beneficial effects on glucose and lipid metabolism that are not shared by other classes of antihypertensive agents. These metabolic actions might only partially be shared by angiotensinconverting enzyme inhibitors. Specific benefits beyond those of other angiotensin receptor blockers have been claimed for telemesartan and, to a lesser extent, irbesartan based on a partial agonist action on PPAR-γ receptors. Although the evidence is strong in vitro, specific actions not shared by other angiotensin receptor blockers have not yet been convincingly demonstrated in vivo or in clinical trials. In many cases, a full range of doses has not been compared, and the apparent superiority of telmesartan could be an artifact of its higher receptor binding affinity, greater tissue penetration owing to lipophilicity, and longer half life.

Astaxanthin lowers blood pressure and lessens the activity of the renin-angiotensin system in Zucker Fatty Rats

“…In particular, we wished to associate the effects of the RAS with BP lowering. Many studies have linked, at least in some manner, the RAS with insulin resistance, obesity, hormonal changes, and the aging phenomenon leading to a hypothesis that activity of the RAS might be as important to these chronic conditions as insulin resistance (Sower et al, 1982;Basso et al, 2005;deCavanagh et al, 2007;Ernsberger & Koletsky, 2007). We selected Zucker Fatty Rats (ZFR) for our animal model as a first approximation, because this rat manifests many of the characteristics making up the metabolic syndrome (Zucker & Zucker, 1961;Bray, 1977;Bach et al, 1981;Talpur et al, 2002).…”

A Systematic Comparison of the Properties of Clinically Used Angiotensin II Type 1 Receptor Antagonists

“…However, the role of PPAR-g in in vivo effects of therapeutic AT1 Receptor Blocker Pharmacology telmisartan doses in patients remains under discussion (Ernsberger and Koletsky, 2007;Rizos et al, 2009). Evidence in favor of this hypothesis includes the findings from many animal models in which typical antihypertensive doses of telmisartan exerted at least some of their effects via PPAR-g, but these animal models may not be predictive for patients.…”

Impaired Function of Dendritic Cells Deficient in Angiotensin II Type 1 Receptors

“…The use of AT 1 antagonist does not guarantee a complete inhibition of AT 1 along the process of DC differentiation. On the other hand, AT 1 blockers are suspected to interact with receptors other than AT 1 , such as peroxisome proliferator-activated receptor-␥ (Schupp et al, 2004;Marshall el al., 2006;Ernsberger and Koletsky, 2007), thromboxane A2/prostaglandin H2 receptors (Liu et al, 1992), and formyl-Met-Leu-Phe receptor (Raiden et al, 1997). Thus, they might not be considered as the most appropriate tool to define the contribution of AT 1 in DC physiology.…”