title: Acute and chronic effects of free radicals on alpha1-adrenergic-induced vasoconstriction in mesenteric beds of spontaneously hypertensive rats.
abstract: OBJECTIVE
  To determine whether free radicals participate in the increased sensitivity of the alpha-adrenergic pathway in mesenteric arteries from spontaneously hypertensive rats (SHRs).
  
  
  RESULTS
  SHRs are characterized by a greater vasoconstriction (P < 0.001) in response to phenylephrine in isolated and perfused mesenteric arteries. Deferoxamine (DFX) produced a significant increase in the phenylephrine-induced vasoconstriction in isolated mesenteric beds from both SHRs (P < 0.001) and Wistar-Kyoto (WKY) rats (P < 0.05), but with a greater magnitude in SHRs (P < 0.01). Acutely, activation of the hypoxanthine-xanthine oxidase (HX-XO) system produced an endothelium- and NO-dependent vasoconstriction at low concentration (P < 0.01), followed by an endothelium-independent vasorelaxation at greater concentrations in phenylephrine-preconstricted mesenteric beds (P < 0.01). Catalase and SOD (P < 0.01) prevented this endothelium-dependent response, whereas the endothelium-independent vasorelaxation induced by HX-XO was blocked by catalase, SOD and DFX (P < 0.01). Chronic administration of a diet deficient in selenium and vitamin E decreased the glutathione peroxidase activity in erythrocytes and plasma from SHRs and WKY rats (P < 0.001). Moreover, the deficient diet significantly increased the sensitivity of mesenteric arteries to phenylephrine in SHRs (P < 0.001) and WKY rats (P < 0.05), whereas it decreased acetylcholine-induced vasodilatation in SHRs only (P < 0.05). The KCl-induced vasoconstriction in response to oxygen radicals was enhanced only in mesenteric bed from SHRs.
  
  
  CONCLUSIONS
  Free radicals seem to potentiate the alpha-adrenergic pathway acutely in low concentrations and to sensitize this pathway chronically in SHRs. These observations may explain the potentiated response to alpha-adrenergic agonists observed in SHRs.
authors.affiliation: Research Group on Autonomic Nervous System, Department of Physiology, Faculty of Medicine, University of Montreal, Montreal (Quebec), Canada.
authors.forename: Hélène
authors.initials: H
authors.lastname: Girouard
authors.forename: Jacques
authors.initials: J
authors.lastname: de Champlain
mesh_terms: D000208:Acute Disease; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001794:Blood Pressure; D001835:Body Weight; D002908:Chronic Disease; D005609:Free Radicals / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D012643:Selenium / Q000494:pharmacology; D013152:Splanchnic Circulation / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D005609:Free Radicals; D016877:Oxidants; D018340:Receptors, Adrenergic, alpha-1; D014662:Vasoconstrictor Agents; D014810:Vitamin E; D010656:Phenylephrine; D011189:Potassium Chloride; D005979:Glutathione Peroxidase; D012643:Selenium