We investigated whether high-fat diet (HFD)-induced obesity was associated with modifications in mesenteric innervation function, the mechanisms involved, and the possible effects of aerobic exercise training on these changes.
Male Wistar rats were divided into three groups: rats fed a standard diet (control group); rats fed a HFD (35% fat) for 8 weeks; and HFD rats submitted to aerobic exercise training (8 weeks, 5 times per week for 50 min). Segments of isolated mesenteric arteries were exposed to electric field stimulation (EFS) with or without phentolamine, suramin, or Nω nitro-L-arginine methyl ester. Noradrenaline, ATP, and nitric oxide release, and total and phosphorylated neuronal nitric oxide synthase (nNOS, P-nNOS) expression were also measured.
EFS contraction was greater in sedentary HFD than in control rats. Phentolamine reduced EFS contractions more markedly in HFD rats. Suramin decreased EFS contractions only in control rats. Phentolamine + suramin practically abolished EFS-induced contraction in control rats, whereas it did not modify it in the HFD rats. Noradrenaline release was greater and ATP was lower in HFD rats. Nω nitro-L-arginine methyl ester increased contractions to EFS only in segments from control rats. Nitric oxide release and nNOS and P-nNOS expressions were lower in arterial segments from HFD rats than from control rats. None of these changes in sedentary HFD rats was present in the trained HFD rats.
Enhanced sympathetic and diminished nitrergic components contributed to increased vasoconstrictor responses to EFS in sedentary HFD rats. All these changes were avoided by aerobic exercise training, suggesting that aerobic exercise could reduce peripheral vascular resistance in obesity.
Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid and Instituto de Investigación La Paz, IdIPAZ, Madrid, Spain
*Esther Sastre and Laura Caracuel contributed equally to the writing of this article.
Correspondence to Dr Javier Blanco-Rivero, Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo, 4, 28029 Madrid, Spain. Tel: +34 1 4975446; fax: +34 1 4975478; e-mail: firstname.lastname@example.org
Abbreviations: CGRP, calcitonin gene-related peptide; DEA-NO, diethylamine NONOate; EFS, electric field stimulation; KHS, Krebs–Henseleit solution; L-NAME, Nω nitro-L-arginine methyl ester; nNOS, neuronal nitric oxide synthase; TTX, tetrodotoxin
Received 14 July, 2014
Revised 13 April, 2015
Accepted 13 April, 2015