Background:

Resorcinolnaphthalein is an Angiotensin-converting enzyme 2 (ACE2) activator [1].

Angiotensin-converting enzyme 2 (ACE2) has been involved in hydrolyzing angiotensin II and opposing its actions, and plays a protective role in the pathogenesis of pulmonary arterial hypertension (PAH) [2]. Targeted disruption of ACE2 in mice results in a severe cardiac contractility defect, increased angiotensin II levels, and upregulation of hypoxia-induced genes in the heart [2].

In vitro: Resorcinolnaphthalein enhanced ACE2 activity in a dose-dependent manner [1].

In vivo: Resorcinolnaphthalein caused significant activation of ACE2 in both normal and diseased rats in 7 days after treatment. Treatment with resorcinolnaphthalein prevented high PAP, right ventricular hypertrophy and neointimal formation. Resorcinolnaphthalein caused an improved endothelia-dependent vasorelaxation and decreased in proinflammatory cytokines, such as TNF-α, MCp-1, IL-6, and increased in anti-inflammatory cytokine IL-10 in the early stage of the pathogenesis [3]. Resorcinolnaphthalein can specifically and effectively enhanced ACE2 activity in rats [4]. ACE2 activation by resorcinolnaphthalein showed effects on pulmonary endothelial dysfunction and neointimal formation during the development of severe PAH in rats [4].

参考文献:
[1] Prada J A H, Ferreira A J, Katovich M J, et al.  Structure-based identification of small-molecule angiotensin-converting enzyme 2 activators as novel antihypertensive agents[J]. Hypertension, 2008, 51(5): 1312-1317.
[2] Crackower M A, Sarao R, Oudit G Y, et al.  Angiotensin-converting enzyme 2 is an essential regulator of heart function[J]. Nature, 2002, 417(6891): 822-828.
[3] Haber P K, Ye M, Wysocki J, et al.  Angiotensin-converting enzyme 2–independent action of presumed angiotensin-converting enzyme 2 activatorsNovelty and significance[J]. Hypertension, 2014, 63(4): 774-782.
[4] Li G, Liu Y, Zhu Y, et al.  ACE2 activation confers endothelial protection and attenuates neointimal lesions in prevention of severe pulmonary arterial hypertension in rats[J]. Lung, 2013, 191(4): 327-336.