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CARDIOVASCULAR

Endocannabinoid Regulates Blood Pressure via Activation of the Transient Receptor Potential Vanilloid Type 1 in Wistar Rats Fed a High-Salt Diet

Departments of Medicine (Y.W., D.H.W.) and Pharmacology and Toxicology (N.E.K.), Michigan State University, East Lansing, Michigan

This study was designed to examine the role of the endocannabinoids in blood pressure regulation during high sodium (HS) intake. HS (4% Na⁺ by weight) intake for 3 weeks increased baseline mean arterial pressure (MAP, mm Hg) compared with normal sodium (NS, 0.4% Na⁺ by weight)-treated male Wistar rats. Capsazepine (3 mg/kg), a selective transient receptor potential vanilloid type 1 (TRPV1) antagonist, caused a greater increase in MAP (mm Hg) in HS-treated compared with NS-treated rats (13 ± 3 versus 4 ± 2, p < 0.05), whereas calcitonin gene-related peptide (CGRP) dose-dependently decreased MAP in both HS- and NS-treated rats with a more profound effect in the former. HS increased plasma anandamide levels analyzed by liquid chromatography/electrospray tandem mass spectrometry (NS, 2.40 ± 0.31 versus HS, 4.05 ± 0.47 pmol/ml, p < 0.05) and plasma CGRP levels determined by radioimmunoassay (NS, 36.6 ± 3.8 versus HS, 55.7 ± 6.4 pg/ml, p < 0.05). Methanandamide, a metabolically stable analog of anandamide, caused a greater CGRP release in mesenteric arteries isolated from HS-treated compared with NS-treated rats. Western blot showed that expression of receptor activity-modifying protein 1, a subunit of the CGRP receptor, in mesenteric arteries was greater in HS-treated compared with NS-treated rats. These results show that HS intake increases production of anandamide, which may serve as an endovanilloid to activate TRPV1, leading to release of CGRP to blunt salt-induced increases in blood pressure. These data support the notion that TRPV1 may act as a molecular target for salt-induced elevation of endovanilloid compounds to regulate blood pressure.

Address correspondence to: Dr. Donna H. Wang, Department of Medicine, B316 Clinical Center, Michigan State University, East Lansing, MI 48824. E-mail: donna.wang{at}ht.msu.edu

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