Tatchum-Talom R, Martin D S
Division of Basic Biomedical Sciences, University of South Dakota School of Medicine, Vermillion 57069, USA.
Can J Physiol Pharmacol. 2004 Mar;82(3):200-7. doi: 10.1139/y04-010.
Ageing is associated with structural and functional alterations of the vasculature. The nature of age-related vascular disorders is not completely understood. Oxidative stress is hypothesized to play a crucial role in the pathophysiology of vascular complications. We investigated the effects of chronic treatment with the superoxide dismutase mimetic tempol (4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl) on vascular function in the mesenteric vasculature of aged rats. Young (3 weeks) and old (40 weeks) Sprague-Dawley rats were treated with tempol (1 mM in drinking water) or vehicle for 3 weeks. Arterial blood pressure was slightly, but significantly, higher in old than in young rats. Tempol had no effect on arterial blood pressure. The vasoconstrictor responses to norepinephrine (NE) and serotonin (5-HT) were exaggerated in the mesenteric vascular bed (MVB) removed from old rats. Vasodilator responses to acetylcholine (ACh), papaverine (PPV), and isoprenaline (ISO) were reduced in the MVB of old rats in comparison with young rats. Chronic treatment of old rats with tempol normalized their responses to NE and 5-HT. The dilator responses to ACh, PPV, and ISO were similar between old rats receiving tempol and young rats. The present findings suggest that oxidative stress contributes to vascular dysfunction in the mesentery of old rats. The vasculoprotective effects of tempol remain to be elucidated.
衰老与脉管系统的结构和功能改变相关。与年龄相关的血管疾病的本质尚未完全明了。氧化应激被认为在血管并发症的病理生理学中起关键作用。我们研究了用超氧化物歧化酶模拟物tempol（4-羟基-2,2,6,6-四甲基哌啶氮氧自由基）长期处理对老年大鼠肠系膜脉管系统血管功能的影响。将年轻（3周龄）和老年（40周龄）的Sprague-Dawley大鼠用tempol（饮水中含1 mM）或赋形剂处理3周。老年大鼠的动脉血压略高于年轻大鼠，但差异显著。Tempol对动脉血压无影响。从老年大鼠分离出的肠系膜血管床（MVB）对去甲肾上腺素（NE）和5-羟色胺（5-HT）的血管收缩反应增强。与年轻大鼠相比，老年大鼠MVB对乙酰胆碱（ACh）、罂粟碱（PPV）和异丙肾上腺素（ISO）的血管舒张反应减弱。用tempol长期处理老年大鼠可使其对NE和5-HT的反应恢复正常。接受tempol处理的老年大鼠与年轻大鼠对ACh、PPV和ISO的舒张反应相似。目前研究结果表明氧化应激促成老年大鼠肠系膜血管功能障碍。Tempol的血管保护作用仍有待阐明。
