Increased depressor response to N-arachidonoyl-dopamine during high salt intake: role of the TRPV1 receptor.J Hypertens. 2007 Dec; 25(12):2426-33.JH
This study was designed to test the hypothesis that the systemic administration of N-arachidonoyl-dopamine (NADA), an endovanilloid, causes a depressor effect via activation of transient receptor potential vanilloid type 1 (TRPV1) channels during high-salt intake.
Wistar rats were fed a normal (0.4%) or high (4%) sodium diet for 10 days, and arteries and veins were cannulated for measurement of mean arterial pressure (MAP) or injection of drugs and collection of plasma. Radioimmunoassay and western blot were used to determine the plasma calcitonin gene-related peptide (CGRP) level and TRPV1 protein content, respectively.
The NADA-induced dose-dependent decrease in MAP was greater in high-sodium than normal-treated rats, and was abolished by capsazepine, a selective TRPV1 antagonist, or CGRP8-37, a selective CGRP receptor antagonist, but not by SR141716A, a selective cannabinoid 1 receptor antagonist. Capsaicin, a selective TRPV1 receptor agonist, or CGRP dose-dependently decreased MAP in normal or high-sodium-treated rats, with a greater effect in the latter. Baseline and NADA-induced increases in plasma CGRP levels were higher in high-sodium than normal-treated rats. TRPV1 protein expression in mesenteric arteries was higher in high-sodium than normal-treated rats. In vitro, NADA caused a greater CGRP release from mesenteric arteries of high-sodium than normal-treated rats, which was blocked by capsazepine.
High sodium increases the sensitivity of blood pressure responses to NADA. The enhanced depressor effect induced by NADA during high-sodium intake is prevented by blockade of the TRPV1 or CGRP receptors, but not cannabinoid 1 receptor. High sodium upregulates mesenteric TRPV1 expression, and increases NADA-induced CGRP release in vitro and in vivo.