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 ϩ by weight) intake for 3 weeks increased baseline mean arterial pressure (MAP, mm Hg) compared with normal sodium (NS, 0.4% Na ϩ 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 NStreated rats (13 Ϯ 3 versus 4 Ϯ 2, p Ͻ 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 Ϯ 0.31 versus HS, 4.05 Ϯ 0.47 pmol/ml, p Ͻ 0.05) and plasma CGRP levels determined by radioimmunoassay (NS, 36.6 Ϯ 3.8 versus HS, 55.7 Ϯ 6.4 pg/ml, p Ͻ 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.

TRPV1 Gene Deficiency Attenuates Miniature EPSC Potentiation Induced by Mannitol and Angiotensin II in Supraoptic Magnocellular Neurons

“…Recent studies have demonstrated also that synaptic transmission in the SON is regulated by endocannabinoids (Hirasawa et al, 2004;McDonald et al, 2008). In high-salt diet rats, endocannabinoids regulate blood pressure through activation of the TRPV1 channel (Wang et al, 2007). Considered collectively, these results suggest that endocannabinoids participate in osmoregulation and interact with the TRP channels.…”

Enhanced salt sensitivity following shRNA silencing of neuronal TRPV1 in rat spinal cord

“…Moreover, the depressor effect of TRPV1 activation after capsaicin administration was much greater in HS rats compared with NS rats, supporting the notion that TRPV1 plays a counter-regulatory role against salt-induced increases www.chinaphar.com Yu SQ et al Acta Pharmacologica Sinica npg in blood pressure. The counter-regulatory effect of TRPV1 has been shown to involve enhanced CGRP release from sensory nerves that cause vasodilation, sodium and water excretion, and decreases in blood pressure [39][40][41][42][43] . TRPV1 shRNA treatment resulted in enhanced suppression of mesenteric TRPV1 levels but enhanced up-regulation of mesenteric tyrosine hydroxylase contents.…”

Enhanced function of inhibitory presynaptic cannabinoid CB1 receptors on sympathetic nerves of DOCA–salt hypertensive rats

“…[33,49]). Thus, the plasma level of the endocannabinoid anandamide (AEA) is increased in hypertensive patients [8,21] and animals [21,45]. Moreover, the defective gene variant FAAH 129T of fatty acid amide hydrolase (FAAH; an enzyme responsible for AEA degradation) is associated with lower BP in young males [38].…”