Acute and chronic effects of free radicals on α1-adrenergic-induced vasoconstriction in mesenteric beds of spontaneously hypertensive rats

OBJECTIVE: To determine whether free radicals participate in the increased sensitivity of the alpha-adrenergic pathway in mesenteric arteries from spontaneously hypertensive rats (SHRs). METHODS AND 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. CONCLUSION: 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.