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Obesity decreases the activity of the vascular endocannabinoid system: role of eNOS and AMPK
Author(s) -
Lobato Nubia,
Filgueira Fernando,
Giachini Fernanda,
Carvalho Maria Helena,
Webb Clinton,
Tostes Rita,
Fortes Zuleica
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.570.7
Subject(s) - endocannabinoid system , medicine , endocrinology , ampk , enos , anandamide , chemistry , adenylyl cyclase , cannabinoid receptor , mapk/erk pathway , phosphorylation , protein kinase a , receptor , nitric oxide , nitric oxide synthase , agonist , biochemistry
AIMS Since the endocannabinoid system controls the energy balance and the vascular tone, we evaluated the effects of obesity on the activity of this system in the vessel. METHODS AND RESULTS Vascular function was assessed in small mesenteric arteries from young obese Zucker rats (OZRs) and their lean counterparts (LZRs). The relaxation to anandamide (AEA), to CB1 and CB2 agonists was decreased in OZRs. CB1 and CB2 blockade almost blunted the AEA response in OZRs. The protein expression of these receptors was decreased in OZRs. Inhibition of AEA transport, NO and prostanoids production decreased the relaxation to AEA only in LZRs, indicating impairment of these mechanisms in OZRs. Signaling pathways mediated by adenylyl cyclase, guanylyl cyclase, PI3K, PKG and PKA are not involved in the decreased relaxation to AEA. ERK inhibition restored the AEA relaxation in OZRs. Only in OZRs, the incubation with AEA increased ERK phosphorylation, which was already increased, indicating activation of contracting pathways by AEA in obesity. AMPK activation restored the relaxation to AEA. Incubation with AEA increased the phosphorylation of eNOS, AMPK and acetyl CoA carboxylase only in LZRs, indicating that these proteins mediate the AEA relaxation in LZRs, and this mechanism is impaired in OZRs. CONCLUSION Obesity decreases the activity of the vascular endocannabinoid system by reducing the activity of AMPK and eNOS. FAPESP