Published Online
on September 6, 2005

A more recent version of this article appeared on October 1, 2005

This Article Full Text (PDF) All Versions of this Article: 46/4/986    most recent 01.HYP.0000174596.95607.fdv1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, Y. Articles by Wang, D. H. Search for Related Content PubMed PubMed Citation Articles by Wang, Y. Articles by Wang, D. H. Related Collections Cardiovascular Pharmacology Animal models of human disease

Submitted on April 26, 2005
Revised on May 11, 2005

VR1-Mediated Depressor Effects During High-Salt Intake. Role of Anandamide

Youping Wang^*; Norbert E. Kaminski; and Donna H. Wang

From Department of Medicine and Pharmacology and Toxicology, Michigan State University, East Lansing, Mich.

^* To whom correspondence should be addressed. E-mail: donna.wang{at}ht.msu.edu.

Abstract--This study was designed to test the hypothesis that increased sensitivity of blood pressure to anandamide (AEA), an endocannabinoid compound, occurs during high-salt intake, which can be blocked by a selective vanilloid receptor 1(VR1) antagonist, capsazepine (CAPZ). Intravenous administration of a metabolically stable analog, methanandamide (MethA), dose-dependently decreased mean arterial pressure (MAP) in conscious rats fed a high-sodium diet (HS) for 3 weeks but it had a minimal effect in normal sodium (NS)-treated rats. The MethA-induced decrease in MAP was significantly attenuated but not abolished by CAPZ, or a selective cannabinoid receptor 1 (CB1) antagonist, SR141716A, administered separately in HS-treated rats. The MethA-induced depressor effect was prevented by the combined administration of CAPZ and SR141716A in HS-treated rats. Likewise, administration of capsaicin, a selective VR1 receptor agonist, dose-dependently decreased MAP in both HS- and NS-treated rats. The depressor effect of capsaicin was more profound in HS-treated rats, which was prevented by CAPZ. Western blot showed that expression of VR1 but not CB1 in mesenteric arteries was increased in HS-treated compared with NS-treated rats. Therefore, these data show that: (1) HS upregulates mesenteric VR1 expression; (2) HS increases sensitivity of blood pressure to AEA; and (3) HS-induced enhancement of the depressor effect of AEA can be prevented only when both VR1 and CB1 receptors are blocked. These results indicate that AEA contributes to the prevention of salt induced increases in blood pressure via, at least in part, activating the VR1 receptor.

Key words: high salt intake • blood pressure • sensory nerves • neurotransmitters

This article has been cited by other articles:

				F. Gao, D. Sui, R. M. Garavito, R. M. Worden, and D. H. Wang Salt Intake Augments Hypotensive Effects of Transient Receptor Potential Vanilloid 4: Functional Significance and Implication Hypertension, February 1, 2009; 53(2): 228 - 235. [Abstract] [Full Text] [PDF]

				Y. Wang, D. Babankova, J. Huang, G. M. Swain, and D. H. Wang Deletion of Transient Receptor Potential Vanilloid Type 1 Receptors Exaggerates Renal Damage in Deoxycorticosterone Acetate-Salt Hypertension Hypertension, August 1, 2008; 52(2): 264 - 270. [Abstract] [Full Text] [PDF]

				Y. Wang, M. Novotny, V. Quaiserova-Mocko, G. M. Swain, and D. H. Wang TRPV1-mediated protection against endotoxin-induced hypotension and mortality in rats Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2008; 294(5): R1517 - R1523. [Abstract] [Full Text] [PDF]

				Y. Wang, N. E. Kaminski, and D. H. Wang Endocannabinoid Regulates Blood Pressure via Activation of the Transient Receptor Potential Vanilloid Type 1 in Wistar Rats Fed a High-Salt Diet J. Pharmacol. Exp. Ther., May 1, 2007; 321(2): 763 - 769. [Abstract] [Full Text] [PDF]

				Y. Wang, A. F. Chen, and D. H. Wang Enhanced oxidative stress in kidneys of salt-sensitive hypertension: role of sensory nerves Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H3136 - H3143. [Abstract] [Full Text] [PDF]

				P. Pacher, S. Batkai, and G. Kunos The Endocannabinoid System as an Emerging Target of Pharmacotherapy Pharmacol. Rev., September 1, 2006; 58(3): 389 - 462. [Abstract] [Full Text] [PDF]

				Y. Wang and D. H. Wang A Novel Mechanism Contributing to Development of Dahl Salt-Sensitive Hypertension: Role of the Transient Receptor Potential Vanilloid Type 1 Hypertension, March 1, 2006; 47(3): 609 - 614. [Abstract] [Full Text] [PDF]