title: Vasorelaxation responses to insulin in laminar vessel rings from healthy, lean horses.
abstract: Hyperinsulinemia causes laminitis experimentally and is a risk factor for naturally occurring laminitis. The aim of this study was to investigate the effects of insulin on laminar vascular relaxation and to induce insulin-associated vascular dysfunction in vitro. Relaxation responses of isolated laminar arterial and venous rings to acetylcholine and insulin were evaluated. To alter vascular function in response to insulin, all vessel rings were incubated with insulin or vehicle, submaximally contracted, administered insulin again and relaxation responses recorded. Laminar arteries were also incubated with the mitogen-activated protein kinase (MAPK) inhibitor, PD-98059. Relaxation in response to acetylcholine was not different between arteries and veins, but veins relaxed less in response to insulin than arteries. In arteries incubated with insulin, the subsequent relaxation response to insulin was blunted. Veins had minimal relaxation to insulin regardless of incubation. Arteries incubated with PD-98059 relaxed more in response to insulin than arteries not exposed to PD-98059, indicating that MAPK plays a role in maintenance of basal tone in laminar arteries. A differing response of laminar veins and arteries to insulin-induced relaxation may be important in understanding the link between hyperinsulinemia and laminitis. In vitro induction of vascular dysfunction in response to insulin in laminar arteries may be useful for testing therapeutic interventions and for understanding the pathophysiology of laminitis.
authors.affiliation: Department of Clinical Sciences, Auburn University College of Veterinary Medicine, 1500 Wire Road, Auburn, Alabama 36849, USA. Electronic address: aaw0002@auburn.edu.
authors.forename: A A
authors.initials: AA
authors.lastname: Wooldridge
authors.affiliation: Southeastern Veterinary Surgery Center, 3576 Macon Rd., Columbus, Georgia 31907, USA.
authors.forename: R W
authors.initials: RW
authors.lastname: Waguespack
authors.affiliation: Department of Anatomy, Physiology, and Pharmacology, Auburn University College of Veterinary Medicine, 1500 Wire Road, Auburn, Alabama 36849, USA.
authors.forename: D D
authors.initials: DD
authors.lastname: Schwartz
authors.affiliation: Equine Health Studies Program, Louisiana State University School of Veterinary Medicine, Skip Bertman Drive, Baton Rouge, Louisiana 70803, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Venugopal
authors.affiliation: Equine Health Studies Program, Louisiana State University School of Veterinary Medicine, Skip Bertman Drive, Baton Rouge, Louisiana 70803, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Eades
authors.affiliation: Equine Health Studies Program, Louisiana State University School of Veterinary Medicine, Skip Bertman Drive, Baton Rouge, Louisiana 70803, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Beadle
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D005528:Foot / Q000098:blood supply; D006736:Horses; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D046509:Tissue Culture Techniques; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D005419:Flavonoids; D007328:Insulin; D014665:Vasodilator Agents; D020929:Mitogen-Activated Protein Kinase Kinases; D000109:Acetylcholine; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: Equine; Insulin; Laminar vessel; Laminitis; Vasorelaxation