The novel peptide apelin regulates intrarenal artery tone in diabetic mice.
Apelin, a newly identified angiotensin (Ang) II homologue, has been implicated in diabetes. We previously reported that apelin exerts an opposing influence on the Ang II signaling. Our aim was to further implore whether apelin could regulate intrarenal artery tone in response to Ang II and Ang IV in diabetes. A Multi Myograph system was used to determine the isometric renal artery tone in diabetic db/db and control db/m+ mice. The phosphorylation, and protein levels of endothelial nitric oxide (NO) synthase (eNOS), and apelin receptor APJ were analyzed by Western blotting. Diminished expression of APJ protein and enhanced contractile responses to Ang II and Ang IV were exhibited in renal arteries from db/db mice. Apelin supplement reversed the abnormal renal vascular responsiveness to Ang II and acetylcholine, but not to Ang IV in db/db mice. Finally, in db/db mice, significant increases in phosphorylation of eNOS on serine 1177 and in NO generation were found in renal arteries pretreated with apelin. Our findings provide novel evidence for the regulatory roles of renal apelin system in vascular functions in diabetes. Apelin treatment may regulate the balance between Ang II and NO and thereby exert beneficial effects on the diabetic vascular pathophysiology.
Zhong
Jiu-Chang
JC
Research Center of Medical Sciences, Guangdong Provincial People's Hospital, Guangdong Provincial Cardiovascular Institute, Guangzhou, Guangdong, China.
Huang
Yu
Y
Yung
Lai-Ming
LM
Lau
Chi-Wai
CW
Leung
Fung-Ping
FP
Wong
Wing-Tak
WT
Lin
Shu-Guang
SG
Yu
Xi-Yong
XY
D000109:Acetylcholine / Q000494:pharmacology; D054392:Adipokines; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D000073861:Apelin; D000075244:Apelin Receptors; D015153:Blotting, Western; D002352:Carrier Proteins / Q000494:pharmacology*; D003920:Diabetes Mellitus / Q000378:metabolism / Q000503:physiopathology*; D007333:Insulin Resistance; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012077:Renal Artery / Q000187:drug effects / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects
D054392:Adipokines; D000073861:Apelin; D000075244:Apelin Receptors; C402826:Apln protein, mouse; C491285:Aplnr protein, mouse; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; D000804:Angiotensin II; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; D052250:Nitric Oxide Synthase Type III; D000109:Acetylcholine