title: Fatty acids impair endothelium-dependent vasorelaxation: a link between obesity and arterial stiffness in very old Zucker rats.
abstract: To analyze age-related interactions between obesity, its associated metabolic disorders, and macrocirculation, we studied large artery stiffness and fatty acid responsiveness in lean and obese Zucker rats, aged 25 (adult) and 80 weeks (very old). Systolic arterial pressure was higher in old obese than in old lean rats (178 ± 10 vs 134 ± 8 mmHg, respectively). Carotid elastic modulus-wall stress curves showed increased age-dependent arterial stiffening, which was greater in obese animals. Old obese exhibited endothelial dysfunction with increased systemic oxidative stress. Adult obese had elevated plasma free fatty acid levels (1,866 ± 177 vs 310 ± 34 μg/μL in lean animals). In old obese, linoleate and palmitate increased contractility to phenylephrine and reduced relaxation to acetylcholine. Thus, obesity at 25 weeks appears to trigger accelerated arterial aging observed at 80 weeks. The early increase in free fatty acids may be a key effector in the severe arterial stiffness of the aged obese Zucker model.
authors.affiliation: Institut National de la Santé Et de la Recherche Médicale, U961, Vandoeuvre-les-Nancy, France.
authors.forename: Natacha
authors.initials: N
authors.lastname: Sloboda
authors.forename: Bruno
authors.initials: B
authors.lastname: Fève
authors.forename: Simon N
authors.initials: SN
authors.lastname: Thornton
authors.forename: Rosine
authors.initials: R
authors.lastname: Nzietchueng
authors.forename: Véronique
authors.initials: V
authors.lastname: Regnault
authors.forename: Ginny
authors.initials: G
authors.lastname: Simon
authors.forename: Carlos
authors.initials: C
authors.lastname: Labat
authors.forename: Huguette
authors.initials: H
authors.lastname: Louis
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Max
authors.forename: Adeline
authors.initials: A
authors.lastname: Muscat
authors.forename: Mary
authors.initials: M
authors.lastname: Osborne-Pellegrin
authors.forename: Patrick
authors.initials: P
authors.lastname: Lacolley
authors.forename: Athanase
authors.initials: A
authors.lastname: Benetos
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002339:Carotid Arteries / Q000473:pathology / Q000503:physiopathology; D018932:Chemokine CCL2 / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D009765:Obesity / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D018384:Oxidative Stress; D051381:Rats; D011924:Rats, Zucker; D015398:Signal Transduction; D059289:Vascular Stiffness / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*
chemical_list: D015415:Biomarkers; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D005230:Fatty Acids, Nonesterified; D018836:Inflammation Mediators