Apelin modulates aortic vascular tone via endothelial nitric oxide synthase phosphorylation pathway in diabetic mice.
OBJECTIVE
The apelin receptor APJ is a putative receptor protein related to angiotensin (Ang) type 1 receptor. The apelin-APJ system has been implicated in diabetes, but its role in the diabetic vasculature and the mechanisms involved remain unclear. Our aim here was to explore the regulatory role of apelin in the aortic vascular tone in diabetic mice.


METHODS
A Multi Myograph system was used to determine the isometric vessel tone in aortic rings from diabetic db/db and control db/m+ mice. The mRNA, phosphorylation, and protein levels of APJ, Akt, and endothelial nitric oxide synthase (eNOS) were analyzed by reverse transcription-polymerase chain reaction and Western blotting, respectively.


RESULTS
There is depressed expression of APJ, enhanced contractile response to Ang II, and reduced relaxation response to acetylcholine in aortas from db/db mice. Apelin treatment strikingly reversed the altered aortic vascular responsiveness to Ang II and acetylcholine in db/db mice, both of which were abolished by the eNOS inhibitor NG-nitro-L-arginine methyl ester. Finally, in db/db mice, considerable increases in phosphorylation of Akt on serine 473 and of eNOS on serine 1177 were found in aortas pretreated with apelin.


CONCLUSIONS
Apelin treatment modulates the abnormal aortic vascular tone in response to Ang II and acetylcholine by potentiating phosphorylation of Akt and eNOS in diabetic mice, suggesting that the apelin-APJ system might be an important regulator of vascular function in diabetes.
Zhong
Jiu-Chang
JC
Research Center of Medicine Sciences, Guangdong Provincial People's Hospital, Guangdong Provincial Cardiovascular Institute, Guangzhou, Guangdong, and Department of Physiology, Chinese University of Hong Kong, Shatin, China. jiuchangzhong@yahoo.com.cn
Yu
Xi-Yong
XY
Huang
Yu
Y
Yung
Lai-Ming
LM
Lau
Chi-Wai
CW
Lin
Shu-Guang
SG
D000109:Acetylcholine / Q000494:pharmacology; D054392:Adipokines; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta; D000073861:Apelin; D000075244:Apelin Receptors; D015153:Blotting, Western / Q000379:methods; D002352:Carrier Proteins / Q000378:metabolism / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D054392:Adipokines; D000073861:Apelin; D000075244:Apelin Receptors; C402826:Apln protein, mouse; C491285:Aplnr protein, mouse; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D014665:Vasodilator Agents; D000804:Angiotensin II; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester