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Role of Arterial TRPV1 Channels in Metabolic Syndrome
Author(s) -
Ohanyan Vahagn A.,
Shamheart Patricia E.,
Guarini Giacinta,
Talasila Phani K.,
Bratz Ian N.
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.978.12
Subject(s) - trpv1 , capsaicin , medicine , endocrinology , chemistry , agonist , mean arterial pressure , knockout mouse , blood pressure , vasoconstriction , transient receptor potential channel , heart rate , receptor
We have previously shown that TRPV1 channel dependent coronary function is compromised in pigs that have metablic syndrome (MetS). However, mechanisms through which TRPV1 regulates coronary arterial function is not known. To investigate this, we employed genetically modified mice lacking TRPV1 (TRPV1 −/− ), Db/Db and Lean mice to determine if TRPV1 channels modulate arterial function while further investigating the hypothesis that arterial dysfunction in MetS is related to impaired TRPV1 channel contribution. Animals were subjected to in vivo infusions of either the TRPV1 agonist capsaicin or PE to examine the integrated circulatory actions of TRPV1. PE infusion (2.5 and 5 μg/kg) significantly increased mean arterial pressure (MAP) in lean and obese mice, however, PE mediated increase in MAP was blunted in TRPV1 knockout mice, suggesting a role for TRPV1 channels in PE mediated vasoconstriction. Capsaicin (1, 10, 20, 100 μg/kg) dose dependently increased blood pressure (B.P.) in lean mice (5.7 ± 1.6, 11.7 ± 2.1, 25.4 ± 3.4, 51.6 ± 3.9%, respectively) which was attenuated in Db/Db mice (3.4 ± 2.1, 3.9 ± 2.1, 7.0 ± 3.3, 17.9 ± 6.2%, respectively). TRPV1 −/− mice exhibited no B.P. changes at any capsaicin concentrations. The eNOS inhibitor, L‐NAME (10mg/kg), further potentiated the increase in B.P. in both groups at 1, 10, and 20 μg/kg concentrations, with a greater increase in lean vs. Db/Db mice. Furthermore, Western analysis revealed coronary TRPV1 protein expression was reduced ~65% in Db/Db mice compared to controls. Conclusions: TRPV1 channel activation may regulate vascular tone via endothelial and smooth muscle pathways and that vascular dysfunction in Db/Db mice is related to impaired TRPV1 channel function.