title: Change in vascular smooth muscle response to 5-HT due to short- or long-term endothelial denudation of the bovine digital vein.
abstract: Several chronic progressive vascular diseases, such as laminitis, show vasocontractile dysfunction that might evolve into reperfusion injury and/or vessel structural remodelling, which may be traced back to aberrant endothelial function. In the present study, the vasomotor responses of bovine digital veins (BDVs) to 5-hydroxytryptamine (5-HT) were investigated in blood vessels, with and without endothelium present, and in samples deprived of endothelium before or after overnight incubation in tissue culture medium, to evaluate the effects of short- and long-term endothelial damage on vascular smooth muscle (VSM) reactivity. No significant effects were observed in the blood vessels tested immediately after the removal of endothelium. In contrast, a significant increase in VSM reactivity to 5-HT was seen in vessels incubated without endothelium. This long-term change in smooth muscle reactivity was prevented by exposure to the nitric oxide (NO) donor nitroprusside (P < 0.01), suggesting that the long-term lack of inhibitory control exerted by endothelium-derived NO is involved in increased VSM reactivity. The RhoA/ROCK pathway inhibitor fasudil reduced VSM hyper-contractility to ~65% (P < 0.001), the superoxide dismutase-mimetic tempol normalised the vascular response and the non-selective COX-inhibitor indomethacin exerted a moderate inhibitory effect (P < 0.05). Thus, over-activation of the RhoA/ROCK pathway and production of reactive oxygen species could account for VSM hyper-reactivity, triggered by long-term endothelium-deprivation in BDVs, suggesting that these biochemical mechanisms are potential targets for controlling the progressive vasocontractile dysfunction of digital veins in animals affected with laminitis.
authors.affiliation: Department of Veterinary Public Health, Division of Veterinary Pharmacology and Toxicology, University of Bari, Strada Provinciale per Casamassima Km 3, 70010 Valenzano (BA), Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Punzi
authors.affiliation: Department of Veterinary Public Health, Division of Veterinary Pharmacology and Toxicology, University of Bari, Strada Provinciale per Casamassima Km 3, 70010 Valenzano (BA), Italy. Electronic address: chiara.belloli@uniba.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Belloli
authors.affiliation: Ecole Nationale Vétérinaire d'Alfort, Université Paris-Est, 7 avenue du général de Gaulle, 94704 Maisons-Alfort Cedex, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Gogny
authors.affiliation: Oniris, UPSP 5304 de Physiopathologie Animale et Pharmacologie Fonctionnelle, LUNAM Université, Atlanpole-La Chantrerie, BP 40706, F-44307 Nantes, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Desfontis
authors.affiliation: Oniris, UPSP 5304 de Physiopathologie Animale et Pharmacologie Fonctionnelle, LUNAM Université, Atlanpole-La Chantrerie, BP 40706, F-44307 Nantes, France.
authors.forename: Mohamed Y
authors.initials: MY
authors.lastname: Mallem
mesh_terms: D000818:Animals; D002417:Cattle; D004730:Endothelium, Vascular / Q000502:physiology*; D005534:Foot Diseases / Q000473:pathology / Q000503:physiopathology / Q000662:veterinary*; D006724:Hoof and Claw; D007249:Inflammation / Q000662:veterinary; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology; D012701:Serotonin / Q000494:pharmacology*; D014680:Veins / Q000187:drug effects* / Q000473:pathology
chemical_list: D012701:Serotonin
keywords: Bovine digital vein; Cyclooxygenase; Reactive oxygen species; RhoA/ROCK; Vascular smooth muscle