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Reduced endothelium-dependent relaxation to anandamide in mesenteric arteries from young obese Zucker rats.
PLoS One 2013; 8(5):e63449Plos

Abstract

Impaired vascular function, manifested by an altered ability of the endothelium to release endothelium-derived relaxing factors and endothelium-derived contracting factors, is consistently reported in obesity. Considering that the endothelium plays a major role in the relaxant response to the cannabinoid agonist anandamide, the present study tested the hypothesis that vascular relaxation to anandamide is decreased in obese rats. Mechanisms contributing to decreased anandamide-induced vasodilation were determined. Resistance mesenteric arteries from young obese Zucker rats (OZRs) and their lean counterparts (LZRs) were used. Vascular reactivity was evaluated in a myograph for isometric tension recording. Protein expression and localization were analyzed by Western blotting and immunofluorescence, respectively. Vasorelaxation to anandamide, acetylcholine, and sodium nitroprusside, as well as to CB1, CB2, and TRPV1 agonists was decreased in endothelium-intact mesenteric arteries from OZRs. Incubation with an AMP-dependent protein kinase (AMPK) activator or a fatty acid amide hydrolase inhibitor restored anandamide-induced vascular relaxation in OZRs. CB1 and CB2 receptors protein expression was decreased in arteries from OZRs. Incubation of mesenteric arteries with anandamide evoked endothelial nitric oxide synthase (eNOS), AMPK and acetyl CoA carboxylase phosphorylation in LZRs, whereas it decreased phosphorylation of these proteins in OZRs. In conclusion, obesity decreases anandamide-induced relaxation in resistance arteries. Decreased cannabinoid receptors expression, increased anandamide degradation, decreased AMPK/eNOS activity as well as impairment of the response mediated by TRPV1 activation seem to contribute to reduce responses to cannabinoid agonists in obesity.

Authors+Show Affiliations

Department of Biological Sciences, Federal University of Goias, Jatai, GO, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23667622

Citation

Lobato, Nubia S., et al. "Reduced Endothelium-dependent Relaxation to Anandamide in Mesenteric Arteries From Young Obese Zucker Rats." PloS One, vol. 8, no. 5, 2013, pp. e63449.
Lobato NS, Filgueira FP, Prakash R, et al. Reduced endothelium-dependent relaxation to anandamide in mesenteric arteries from young obese Zucker rats. PLoS ONE. 2013;8(5):e63449.
Lobato, N. S., Filgueira, F. P., Prakash, R., Giachini, F. R., Ergul, A., Carvalho, M. H., ... Fortes, Z. B. (2013). Reduced endothelium-dependent relaxation to anandamide in mesenteric arteries from young obese Zucker rats. PloS One, 8(5), pp. e63449. doi:10.1371/journal.pone.0063449.
Lobato NS, et al. Reduced Endothelium-dependent Relaxation to Anandamide in Mesenteric Arteries From Young Obese Zucker Rats. PLoS ONE. 2013;8(5):e63449. PubMed PMID: 23667622.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reduced endothelium-dependent relaxation to anandamide in mesenteric arteries from young obese Zucker rats. AU - Lobato,Nubia S, AU - Filgueira,Fernando P, AU - Prakash,Roshini, AU - Giachini,Fernanda R, AU - Ergul,Adviye, AU - Carvalho,Maria Helena C, AU - Webb,R Clinton, AU - Tostes,Rita C, AU - Fortes,Zuleica B, Y1 - 2013/05/07/ PY - 2013/01/03/received PY - 2013/04/03/accepted PY - 2013/5/14/entrez PY - 2013/5/15/pubmed PY - 2013/12/18/medline SP - e63449 EP - e63449 JF - PloS one JO - PLoS ONE VL - 8 IS - 5 N2 - Impaired vascular function, manifested by an altered ability of the endothelium to release endothelium-derived relaxing factors and endothelium-derived contracting factors, is consistently reported in obesity. Considering that the endothelium plays a major role in the relaxant response to the cannabinoid agonist anandamide, the present study tested the hypothesis that vascular relaxation to anandamide is decreased in obese rats. Mechanisms contributing to decreased anandamide-induced vasodilation were determined. Resistance mesenteric arteries from young obese Zucker rats (OZRs) and their lean counterparts (LZRs) were used. Vascular reactivity was evaluated in a myograph for isometric tension recording. Protein expression and localization were analyzed by Western blotting and immunofluorescence, respectively. Vasorelaxation to anandamide, acetylcholine, and sodium nitroprusside, as well as to CB1, CB2, and TRPV1 agonists was decreased in endothelium-intact mesenteric arteries from OZRs. Incubation with an AMP-dependent protein kinase (AMPK) activator or a fatty acid amide hydrolase inhibitor restored anandamide-induced vascular relaxation in OZRs. CB1 and CB2 receptors protein expression was decreased in arteries from OZRs. Incubation of mesenteric arteries with anandamide evoked endothelial nitric oxide synthase (eNOS), AMPK and acetyl CoA carboxylase phosphorylation in LZRs, whereas it decreased phosphorylation of these proteins in OZRs. In conclusion, obesity decreases anandamide-induced relaxation in resistance arteries. Decreased cannabinoid receptors expression, increased anandamide degradation, decreased AMPK/eNOS activity as well as impairment of the response mediated by TRPV1 activation seem to contribute to reduce responses to cannabinoid agonists in obesity. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/23667622/Reduced_endothelium_dependent_relaxation_to_anandamide_in_mesenteric_arteries_from_young_obese_Zucker_rats_ L2 - http://dx.plos.org/10.1371/journal.pone.0063449 DB - PRIME DP - Unbound Medicine ER -