Borer K E, Bailey S R, Harris P A, Elliott J
Royal Veterinary College, Hatfield, Herts, UK University of Melbourne, Melbourne, Vic., Australia.
J Vet Pharmacol Ther. 2013 Jun;36(3):267-74. doi: 10.1111/j.1365-2885.2012.01423.x. Epub 2012 Jul 4.
The underlying pathophysiological triggers for equine acute laminitis are unknown, although digital vasoconstriction, ischaemia, hypoxia and reperfusion injury may be involved. The contractile responses of isolated equine digital arteries (EDAs), harvested from the hindlimbs of normal horses postmortem at an abattoir, were studied acutely (up to 3 h) under hyperoxic (95% oxygen, 5% CO2 ) and hypoxic (95% nitrogen, 5% CO2 ) conditions in organ baths. Phenylephrine (PHE; 10(-6) m), 5-hydroxytryptamine (5-HT; 10(-7) m) and high potassium (K(+) ; 118 mm) caused contraction in EDAs which was significantly (P<0.0001) enhanced under hypoxic conditions. In contrast, contraction stimulated by 9,11-dideoxy-9α,11α-epoxymethanoprostaglandin F2α (U44069; 3 × 10(-8) m) was not significantly enhanced by hypoxia (P=0.75). Hypoxia-enhanced contraction in response to K(+) was greater (P<0.03) in vessels with a functional endothelium than in vessels in which the endothelium was removed by rubbing. Fasudil (10(-6) to 10(-5) m), a Rho kinase inhibitor, and apocynin (10(-3) to 3 × 10(-3) m), an NADPH oxidase inhibitor, significantly (P ≤ 0.05) inhibited hypoxia-enhanced contraction in response to PHE and 5-HT. In conclusion, hypoxia-enhanced contraction occurred in EDAs. This appears to be partially mediated by reactive oxygen species produced by NAPDH oxidase, which activate Rho kinase to increase calcium sensitisation and enhance smooth muscle contraction.
马急性蹄叶炎潜在的病理生理触发因素尚不清楚，不过可能涉及蹄部血管收缩、局部缺血、缺氧和再灌注损伤。从屠宰场正常马后肢采集的离体马蹄部动脉（EDA），在器官浴槽中于高氧（95%氧气，5%二氧化碳）和低氧（95%氮气，5%二氧化碳）条件下进行急性（长达3小时）研究，观察其收缩反应。去氧肾上腺素（PHE；10⁻⁶ m）、5-羟色胺（5-HT；10⁻⁷ m）和高钾（K⁺；118 mmol）可引起EDA收缩，在低氧条件下收缩显著增强（P<0.0001）。相比之下，9,11-二脱氧-9α,11α-环氧甲前列腺素F2α（U44069；3×10⁻⁸ m）刺激引起的收缩在低氧条件下未显著增强（P = 0.75）。与通过摩擦去除内皮的血管相比，具有功能性内皮的血管对K⁺的低氧增强收缩反应更大（P<0.03）。Rho激酶抑制剂法舒地尔（10⁻⁶至10⁻⁵ m）和NADPH氧化酶抑制剂阿波辛（10⁻³至3×10⁻³ m）可显著（P≤0.05）抑制对PHE和5-HT的低氧增强收缩。总之，EDA发生了低氧增强收缩。这似乎部分由NAPDH氧化酶产生的活性氧介导，活性氧激活Rho激酶以增加钙敏感性并增强平滑肌收缩。
