title: Diminished neurogenic femoral artery vasoconstrictor response in a Zucker obese rat model: differential regulation of NOS and COX derivatives.
abstract: OBJECTIVE
  Peripheral arterial disease is one of the macrovascular complications of type 2 diabetes mellitus. This study addresses femoral artery regulation in a prediabetic model of obese Zucker rats (OZR) by examining cross-talk between endothelial and neural factors.
  
  
  RESULTS
  Arterial preparations from lean (LZR) and OZR were subjected to electrical field stimulation (EFS) on basal tone. Nitric oxide synthase (NOS) and cyclooxygenase (COX) isoform expression patterns were determined by immunohistochemical labelling and Western blotting. Results indicate significantly reduced noradrenergic contractions in preparations from OZR compared with those of LZR. Functional inhibition of endothelial NOS (eNOS) indicated a predominant role of this isoform in LZR and its modified activity in OZR. Neural (nNOS) and inducible NOS (iNOS) were activated and their expression was higher in femoral arteries from OZR. Neurotransmission modulated by large-conductance Ca2+-activated (BKCa) or voltage-dependent (KV) K+ channels did not seem compromised in the obese animals. Endothelial COX-1 and COX-2 were expressed in LZR and an additional adventitial location of COX-2 was also observed in OZR, explaining the higher COX-2 protein levels detected in this group. Prostanoids derived from both isoforms helped maintain vasoconstriction in LZR while in OZR only COX-2 was active. Superoxide anion inhibition reduced contractions in endothelium-intact arteries from OZR.
  
  
  CONCLUSIONS
  Endothelial dysfunction led to reduced neurogenic vasoconstriction in femoral arteries from OZR. In a setting of obesity, NO-dependent nNOS and iNOS dilation activity could be an alternative mechanism to offset COX-2- and reactive oxygen species-mediated vasoconstriction, along with impaired endothelial NO relaxation.
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Martínez
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Medardo
authors.initials: M
authors.lastname: Hernández
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad de Valencia, Valencia, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Novella
authors.affiliation: Departamento de Anatomía y Anatomía Patológica Comparadas, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: María Pilar
authors.initials: MP
authors.lastname: Martínez
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Rosa María
authors.initials: RM
authors.lastname: Pagán
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad de Valencia, Valencia, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Hermenegildo
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Albino
authors.initials: A
authors.lastname: García-Sacristán
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Prieto
authors.affiliation: Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Benedito
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005263:Femoral Artery / Q000503:physiopathology*; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D009765:Obesity / Q000201:enzymology* / Q000503:physiopathology*; D015221:Potassium Channels / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011924:Rats, Zucker; D013481:Superoxides / Q000378:metabolism; D014661:Vasoconstriction
chemical_list: D007527:Isoenzymes; D015221:Potassium Channels; D013481:Superoxides; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases