Role of anandamide transporter in regulating calcitonin gene-related peptide production and blood pressure in hypertension

Objectives To explore the role of anandamide (AEA) transporter in regulating calcitonin gene-related peptide (CGRP) production and blood pressure. Methods and 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. Conclusion 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. J Hypertens 27:1224-1232 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.