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Rosuvastatin restored adrenergic and nitrergic function in mesenteric arteries from obese rats
Author(s) -
BlancoRivero Javier,
de las Heras Natalia,
MartínFernández Beatriz,
Cachofeiro Victoria,
Lahera Vicente,
Balfagón Gloria
Publication year - 2011
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2010.01030.x
Subject(s) - endocrinology , medicine , phentolamine , mesenteric arteries , rosuvastatin , adrenergic , sodium nitroprusside , chemistry , stimulation , nitric oxide , artery , receptor
BACKGROUND AND PURPOSE We investigated whether high‐fat diet (HFD)‐induced obesity was associated with changed function of components of the mesenteric innervation (adrenergic, sensory and nitrergic), the mechanisms involved and the possible effects of rosuvastatin on these changes. EXPERIMENTAL APPROACH Male Wistar rats were divided into three groups. (i) rats fed a standard diet (control group); (ii) rats fed a HFD (33.5% fat) for 7 weeks; and (iii) rats fed a HFD and treated with rosuvastatin (15 mg·kg −1 ·day −1 ) for 7 weeks. Segments of isolated mesenteric arteries were exposed to electric field stimulation (EFS) with or without tetrodotoxin, phentolamine, 7‐nitroindazole (7NI) or N ω nitro‐L‐arginine methyl ester (L‐NAME). Noradrenaline, ATP and NO release, and nNOS expression were also measured. KEY RESULTS EFS induced a greater frequency‐dependent contraction in obese than in control rats. In HFD rats, phentolamine reduced contractions elicited by EFS, but noradrenaline release was greater and ATP release decreased. L‐NAME and 7NI increased contractions to EFS in segments from control rats, but not in those from HFD rats. NO release and nNOS expression were lower in arterial segments from HFD rats than in control rats. All these changes in HFD rats were reversed by treatment with rosuvastatin. CONCLUSIONS AND IMPLICATIONS Neural control of mesenteric vasomotor tone was altered in HFD rats. Enhanced adrenergic and diminished nitrergic components both contributed to increased vasoconstrictor responses to EFS. All these changes were reversed by rosuvastatin, indicating novel mechanisms of statins in neural regulation of vascular tone.