アンジオテンシンII受容体拮抗薬とサルコペニア

ロサルタン（アンジオテンシンII受容体拮抗薬の降圧剤）がサルコペニアに有効というマウスでの動物実験の論文を紹介します。

Burks TN, et al: Losartan restores skeletal muscle remodeling and protects against disuse atrophy in sarcopenia. Sci Transl Med. 2011 May 11;3(82):82ra37.

あまり読み込めていないので申し訳ありませんが、ロサルタンの使用で骨格筋のリモデリング後に繊維化が少なく機能が高いという結果で出ました。また、廃用性筋萎縮に対してもロサルタンの使用がその予防に有効という結果でした。

サルコペニアに対してはACE阻害剤が有効という報告は紹介したことがありますが、アンジオテンシンII受容体拮抗薬が有効という報告は、私は動物実験レベルでもはじめて聞きました。

もちろんすぐにヒトにあてはめるわけにはいきませんが、高血圧のサルコペニア患者の薬物療法では、他に禁忌がなければ、第一選択がACE阻害剤、第二選択（ACE阻害剤が咳などの副作用で使用できない場合）がアンジオテンシンII受容体拮抗薬となるかもしれません。正常血圧のサルコペニアの方に対して、これらの降圧剤を使用する必要はないでしょう。

Abstract
Sarcopenia, a critical loss of muscle mass and function because of the physiological process of aging, contributes to disability and mortality in older adults. It increases the incidence of pathologic fractures, causing prolonged periods of hospitalization and rehabilitation. The molecular mechanisms underlying sarcopenia are poorly understood, but recent evidence suggests that increased transforming growth factor-β (TGF-β) signaling contributes to impaired satellite cell function and muscle repair in aged skeletal muscle. We therefore evaluated whether antagonism of TGF-β signaling via losartan, an angiotensin II receptor antagonist commonly used to treat high blood pressure, had a beneficial impact on the muscle remodeling process of sarcopenic mice. We demonstrated that mice treated with losartan developed significantly less fibrosis and exhibited improved in vivo muscle function after cardiotoxin-induced injury. We found that losartan not only blunted the canonical TGF-β signaling cascade but also modulated the noncanonical TGF-β mitogen-activated protein kinase pathway. We next assessed whether losartan was able to combat disuse atrophy in aged mice that were subjected to hindlimb immobilization. We showed that immobilized mice treated with losartan were protected against loss of muscle mass. Unexpectedly, this protective mechanism was not mediated by TGF-β signaling but was due to an increased activation of the insulin-like growth factor 1 (IGF-1)/Akt/mammalian target of rapamycin (mTOR) pathway. Thus, blockade of the AT1 (angiotensin II type I) receptor improved muscle remodeling and protected against disuse atrophy by differentially regulating the TGF-β and IGF-1/Akt/mTOR signaling cascades, two pathways critical for skeletal muscle homeostasis. Thus, losartan, a Food and Drug Administration-approved drug, may prove to have clinical benefits to combat injury-related muscle remodeling and provide protection against disuse atrophy in humans with sarcopenia.