title: Endocannabinoid regulates blood pressure via activation of the transient receptor potential vanilloid type 1 in Wistar rats fed a high-salt diet.
abstract: 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.
authors.affiliation: Department of Medicine, B316 Clinical Center, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Youping
authors.initials: Y
authors.lastname: Wang
authors.forename: Norbert E
authors.initials: NE
authors.lastname: Kaminski
authors.forename: Donna H
authors.initials: DH
authors.lastname: Wang
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000096:biosynthesis / Q000494:pharmacology; D001794:Blood Pressure; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators / Q000502:physiology*; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D063388:Endocannabinoids; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D053284:Polyunsaturated Alkamides; D051381:Rats; D017208:Rats, Wistar; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D050916:TRPV Cation Channels / Q000502:physiology*
chemical_list: D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D017673:Sodium Chloride, Dietary; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C088155:methanandamide; D015740:Calcitonin Gene-Related Peptide; C071423:capsazepine; D002211:Capsaicin; C078814:anandamide