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.
Footnotes
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This study was supported in part by the National Institute of Health (Grants HL-57853, HL-73287, and DK67620) and by a grant from Michigan Economic Development Corporation. D.H.W. is an Established Investigator of the American Heart Association.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.106.112904.
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ABBREVIATIONS: TRPV1, transient receptor potential vanilloid type 1; CGRP, calcitonin gene-related peptide; CB1, cannabinoid receptor type 1; CB2, cannabinoid receptor type 2; CAPZ, capsazepine; HS, high sodium; NS, normal sodium; MAP, mean arterial pressure; HR, heart rate; MethA, methanandamide; CRLR, calcitonin receptor-like receptor; RAMP, receptor activity-modifying protein.
- Received August 23, 2006.
- Accepted February 13, 2007.
- The American Society for Pharmacology and Experimental Therapeutics
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