Apelin activates L-arginine/nitric oxide synthase/nitric oxide pathway in rat aortas.
Apelin was recently found to be an inotropic polypeptide in isolated rat hearts, and intravenous injection of apelin can induce a transient decrease in blood pressure. To illustrate the mechanism of apelin-induced vasodilation, we observed the in vitro effects of apelin on the L-arginine (L-Arg)/nitric oxide (NO) pathway in the incubated, isolated rat aorta. Apelin stimulated vascular NO(2)(-) product and NOS activation in a concentration- and time-dependent manner. Compared with no apelin treatment, incubation with apelin (10(-9), 10(-8), and 10(-7)mol/L) increased NO(2)(-) product by 33%, 46%, and 69% (all p<0.01), respectively, and Ca(2+)-dependent constitutive NOS (cNOS) activity by 200%, 460%, and 550% (all p<0.01), respectively. However, Ca(2+)-independent NOS (iNOS) activity was not significantly altered (p>0.05). Apelin incubation (10(-9), 10(-8), and 10(-7)mol/L) increased L-Arg uptake by 130%, 180%, and 240% (all p<0.01), respectively. The mRNA level of cationic amino acid transporters, CAT-1 and CAT-2B, in rat aortic tissues treated with 10(-7)mol/L apelin was increased by 110% and 128%, respectively (both p<0.01). Incubation with 10(-7)mol/L apelin elevated eNOS mRNA and protein levels, by 53% (p<0.05) and 319% (p<0.01), respectively. Collectively, these results demonstrate that apelin directly activated the vascular L-Arg/NOS/NO pathway, which could be one of the important mechanisms of apelin-regulated vascular function.
Jia
Yue Xia
YX
Institute of Cardiovascular Research, Peking University First Hospital, Beijing 100034, China.
Lu
Zheng Fei
ZF
Zhang
Jing
J
Pan
Chun Shui
CS
Yang
Jing Hui
JH
Zhao
Jing
J
Yu
Fang
F
Duan
Xiao Hui
XH
Tang
Chao Shu
CS
Qi
Yong Fen
YF
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D000073861:Apelin; D001120:Arginine / Q000378:metabolism*; D001483:Base Sequence; D002352:Carrier Proteins / Q000494:pharmacology*; D002374:Catalase / Q000235:genetics; D017931:DNA Primers; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000073861:Apelin; C498579:Apln protein, rat; D002352:Carrier Proteins; D017931:DNA Primers; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D009569:Nitric Oxide; D001120:Arginine; D002374:Catalase; D019001:Nitric Oxide Synthase