Effects of all-trans retinoic acid on orphan receptor APJ signaling in spontaneously hypertensive rats

doi:10.1016/j.cardiores.2004.10.020

Cardiovascular Research 2005 65(3):743-750; doi:10.1016/j.cardiores.2004.10.020

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Effects of all-trans retinoic acid on orphan receptor APJ signaling in spontaneously hypertensive rats

Jiu-Chang Zhong^a^,*, Dong-Yang Huang^a^,*, Ge-Fei Liu^a, Hai-Yan Jin^b, Yan-Mei Yang^a, Yi-Fan Li^a, Xu-Hong Song^a and Kun Du^a

^aCenter for Molecular Biology, Shantou University Medical College, 22 Xin Ling Rd., Shantou, Guangdong 515041, China
^bInstitute of Cardiovascular Research, Guangdong Provincial People's Hospital, Guangzhou, Guangdong 510080, China

^* Corresponding authors. Tel.: +86 754 8900400; fax: +86 754 8557562. Email address: g_jczhong{at}stu.edu.cn huangdy{at}stu.edu.cn

Objective: Studies show general agreement that all-trans retinoicacid (atRA) has been linked to the regulation of G protein-coupledreceptor (GPCRs) signaling. To further validate effects of atRAon the cardiovascular GPCRs, the present study was designedto assess whether atRA will modulate orphan receptor APJ, ahomologue of angiotensin II type 1 (AT₁) receptor.

Methods: Real-time polymerase chain reaction and Western blotmethods were performed to examine the expression of APJ andits endogenous ligand apelin in spontaneously hypertensive rats(SHR) and Wistar–Kyoto (WKY) rats after chronic atRA treatment.

Results: APJ and apelin expression were markedly depressed inplacebo-treated SHR, compared with WKY rats (p<0.01). However,in atRA-treated SHR, a significant upregulation of APJ and apelinexpression was observed in both heart and aorta (p<0.05),accompanied by a reduction of AT₁ expression, an elevation ofserum nitric oxide levels and a subsequent decrease of bloodpressure.

Conclusions: Chronic atRA treatment activates gene and proteinexpression of APJ and apelin and reduces blood pressure in SHR,suggesting that atRA may regulate the balance between apelin-APJand angiotensin II-AT₁ signaling and have potential clinicalvalue in the prevention and treatment of human hypertension.

KEYWORDS All-trans retinoic acid; Hypertension; APJ; Apelin; Nitric oxide

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