Changes in plasma oxidative state with age and their influence on contractions elicited by noradrenaline in the rat tail artery.
The present study analyzes the changes in plasma oxidative state with age and their influence on the contractions induced by noradrenaline (NA) in endothelium-denuded segments from the tail artery of 6- (young), 24- (old) and 30- (very old) month-old Sprague Dawley rats. The sensitivity (-log EC50) to NA increased with age, this increase being higher in old than in very old animals. Moreover, the maximum response (Emax) to NA did not change in old rats, whereas decreased in very old animals. We also found a progressive increase in the plasma oxidative state with age, measured as malondialdehyde (MDA) levels, that was accompanied by a decrease in the plasma antioxidative state, measured as glutathione peroxidase activity. In addition, MDA (0.5, 1 and 10 microM) potentiated the NA responses in 6-, 24- and 30-month-old rats, respectively, without affecting Emax. In young animals, catalase (1000 U/ml) or dimethylsulfoxide (7 mM), scavengers of hydrogen peroxide or hydroxyl radicals, respectively, did not modify either the contractions induced by NA in control situation or the potentiation of these responses caused by MDA. However, the superoxide anion scavenger, superoxide dismutase (SOD, 150 U/ml), completely reversed the increase in sensitivity to NA caused by MDA, without affecting NA responses in control situation. These results suggest that the increase in NA sensitivity with age could be due, at least in part, to the enhancement of plasma oxidative state during aging. In addition, in this alteration of the responses to NA caused by MDA, the generation of superoxide anions appears to be involved. This study supports the hypothesis that the enhancement of plasma oxidative state could play an important role in the increase of vascular resistance with age.
Rodríguez-Martínez
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MA
Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Spain.
García-Cohen
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EC
Briones
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Baena
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Marín
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Salaices
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Marín
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D000375:Aging / Q000502:physiology*; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology*; D002374:Catalase / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology; D016166:Free Radical Scavengers / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000097:blood; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D009638:Norepinephrine / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D013623:Tail / Q000098:blood supply; D014661:Vasoconstriction / Q000187:drug effects*
D016166:Free Radical Scavengers; D008315:Malondialdehyde; D011189:Potassium Chloride; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D009638:Norepinephrine