Role of anandamide transporter in regulating calcitonin  gene-related peptide production and blood pressure  in hypertension.
OBJECTIVE
To explore the role of anandamide (AEA) transporter in regulating calcitonin gene-related peptide (CGRP) production and blood pressure.


RESULTS
Plasma levels of AEA, CGRP, asymmetric dimethylarginine (ADMA) and nitric oxide in patients with essential hypertension, spontaneously hypertensive rats (SHRs) and 2 kidney 1 clip hypertensive rats and the CGRP mRNA expression in dorsal root ganglion of rats were measured. Peripheral blood lymphocytes were isolated to examine the AEA transporter activity, the role of AEA transporter in regulating CGRP mRNA expression or the effect of exogenous ADMA on AEA transporter activity. In both hypertensive patients and SHRs, the plasma level of AEA was elevated, but the AEA transporter activity was attenuated concomitantly with decreased CGRP production. Moreover, plasma ADMA level in SHRs was elevated accompanied by decreased nitric oxide level. By contrast, the plasma AEA level was elevated accompanied by increased CGRP production in 2 kidney 1 clip hypertensive rats, and there were no significant changes in plasma levels of ADMA, nitric oxide and the AEA transporter activity. In vitro, exogenous administration of AEA upregulated CGRP mRNA expression in lymphocytes, which was inhibited by AEA transporter blocker, AM404, and the AEA transporter activity was reduced by ADMA.


CONCLUSIONS
Decreased plasma CGRP level in patients with essential hypertension or SHRs is likely due to the reduced AEA transporter activity, and the increased ADMA level may account for the reduced AEA transporter activity.
Li
Dai
D
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China.
Chen
Ben-Mei
BM
Peng
Jun
J
Zhang
Yi-Shuai
YS
Li
Xiao-Hui
XH
Yuan
Qiong
Q
Hu
Chang-Ping
CP
Deng
Han-Wu
HW
Li
Yuan-Jian
YJ
D000818:Animals; D001095:Arachidonic Acids / Q000097:blood* / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology; D001483:Base Sequence; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000097:blood*; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D063388:Endocannabinoids; D005727:Ganglia, Spinal / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D006978:Hypertension, Renovascular / Q000235:genetics / Q000503:physiopathology; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D053284:Polyunsaturated Alkamides / Q000097:blood*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar
D001095:Arachidonic Acids; D002352:Carrier Proteins; D017931:DNA Primers; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D012333:RNA, Messenger; C018524:N,N-dimethylarginine; D001120:Arginine; D015740:Calcitonin Gene-Related Peptide; C078814:anandamide; C107594:N-(4-hydroxyphenyl)arachidonylamide