Effects of all-trans retinoic acid on orphan receptor APJ signaling in spontaneously hypertensive rats.
OBJECTIVE
Studies show general agreement that all-trans retinoic acid (atRA) has been linked to the regulation of G protein-coupled receptor (GPCRs) signaling. To further validate effects of atRA on the cardiovascular GPCRs, the present study was designed to assess whether atRA will modulate orphan receptor APJ, a homologue of angiotensin II type 1 (AT(1)) receptor.


METHODS
Real-time polymerase chain reaction and Western blot methods were performed to examine the expression of APJ and its 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 in placebo-treated SHR, compared with WKY rats (p<0.01). However, in atRA-treated SHR, a significant upregulation of APJ and apelin expression was observed in both heart and aorta (p<0.05), accompanied by a reduction of AT(1) expression, an elevation of serum nitric oxide levels and a subsequent decrease of blood pressure.


CONCLUSIONS
Chronic atRA treatment activates gene and protein expression of APJ and apelin and reduces blood pressure in SHR, suggesting that atRA may regulate the balance between apelin-APJ and angiotensin II-AT(1) signaling and have potential clinical value in the prevention and treatment of human hypertension.
Zhong
Jiu-Chang
JC
Center for Molecular Biology, Shantou University Medical College, Shantou, Guangdong 515041, China. g_jczhong@stu.edu.cn
Huang
Dong-Yang
DY
Liu
Ge-Fei
GF
Jin
Hai-Yan
HY
Yang
Yan-Mei
YM
Li
Yi-Fan
YF
Song
Xu-Hong
XH
Du
Kun
K
D000818:Animals; D000073861:Apelin; D000075244:Apelin Receptors; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014212:Tretinoin / Q000097:blood / Q000494:pharmacology*
D000073861:Apelin; D000075244:Apelin Receptors; C498579:Apln protein, rat; C491284:Aplnr protein, rat; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D043562:Receptors, G-Protein-Coupled; D009569:Nitric Oxide; D014212:Tretinoin