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血管紧张素受体拮抗剂的代谢作用:过氧化物酶体增殖物激活受体γ激动剂作用还是类效应?

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

作者信息

Ernsberger Paul, Koletsky Richard J

机构信息

Department of Nutrition, Case Western Reserve University, School of Medicine, Cleveland, OH 44106-4906, USA.

出版信息

Curr Opin Pharmacol. 2007 Apr;7(2):140-5. doi: 10.1016/j.coph.2006.11.008. Epub 2007 Feb 15.

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 angiotensin-converting 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-gamma 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.

摘要

越来越多的基础和临床数据支持这样一种假说,即血管紧张素受体阻滞剂对葡萄糖和脂质代谢具有有益作用,而其他类别的抗高血压药物则没有这种作用。血管紧张素转换酶抑制剂可能仅部分具有这些代谢作用。替米沙坦以及在较小程度上厄贝沙坦基于对过氧化物酶体增殖物激活受体γ(PPAR-γ)的部分激动作用,被认为具有超越其他血管紧张素受体阻滞剂的特定益处。尽管体外证据充分,但其他血管紧张素受体阻滞剂未共享的特定作用尚未在体内或临床试验中得到令人信服的证明。在许多情况下,尚未比较全剂量范围,替米沙坦的明显优势可能是由于其较高的受体结合亲和力、因亲脂性而具有的更大组织穿透力以及更长的半衰期造成的假象。

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