Tempol improves vascular function in the mesenteric vascular bed of senescent rats.
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.
Tatchum-Talom
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Division of Basic Biomedical Sciences, University of South Dakota School of Medicine, Vermillion 57069, USA.
Martin
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DS
D000284:Administration, Oral; D000375:Aging / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001835:Body Weight; D003497:Cyclic N-Oxides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006321:Heart / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D010208:Papaverine / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D003497:Cyclic N-Oxides; D013113:Spin Labels; D012701:Serotonin; D010208:Papaverine; D013482:Superoxide Dismutase; C001803:tempol; D009638:Norepinephrine