Intermedin1-53 activates L-arginine/nitric oxide synthase/nitric oxide pathway in rat aortas.
Intermedin (IMD), a novel member of the calcitonin/calcitonin gene-related peptide (CGRP) family, has similar or more potent vasodilatory and hypotensive actions than adrenomedullin (ADM) and CGRP. The present study was designed to observe the effects of synthetic rat IMD1-53 on L-arginine (L-Arg) cellular transport, nitric oxide synthase (NOS) activity, and nitric oxide (NO) production in the isolated rat aortic ring to illustrate its direct effect on the L-Arg/NOS/NO pathway in vasculature. IMD1-53 significantly increased NO production and cNOS activity in rat aortas and was more potent than equivalent ADM. But the peptides of both IMD and ADM had no effect on inducible NOS expression and activity. Otherwise, IMD1-53 induced a concentration-dependent increase in [3H]L-Arg transport and its effect was more potent than that of an equivalent concentration of ADM. Semiquantitative RT-PCR revealed that IMD1-53 significantly increased cationic amino acid transport (CAT)-1 and CAT-2B mRNA expression, and its effect was similar to that of ADM. All these results suggest that IMD1-53 might regulate vessel function homeostasis via upregulating the L-Arg/NOS/NO pathway.
Yang
Jing-Hui
JH
Institute of Cardiovascular Research, Peking University First Hospital, Beijing 100034, China.
Pan
Chun-Shui
CS
Jia
Yue-Xia
YX
Zhang
Jing
J
Zhao
Jing
J
Pang
Yong-Zheng
YZ
Yang
Jun
J
Tang
Chao-Shu
CS
Qi
Yong-Fen
YF
D053607:Adrenomedullin; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001120:Arginine / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D006706:Homeostasis; D008297:Male; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015854:Up-Regulation
C499411:Adm2 protein, rat; D000596:Amino Acids; D009479:Neuropeptides; D010455:Peptides; D012333:RNA, Messenger; D053607:Adrenomedullin; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase