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      Methylene Blue Restores Vasodilation to Bradykinin after Inhibition of Nitric Oxide Production in the Isolated Dog Lung

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          Methylene blue (MB) is a widely used putative inhibitor of nitric oxide (NO)-dependent responses, particularly in cell culture and vascular ring studies. MB is postulated to diminish vasodilation to NO either by preventing activation of guanylate cyclase by NO or by oxidizing NO formed by NO synthase. In the present study we examined whether MB inhibited vasodilation to bradykinin (BK) in the cyclooxygenase-inhibited, isolated canine lung lobe perfused with blood at constant flow. One group of lobes (n = 5) was challenged with BK at baseline vascular tone, after tone was doubled by infusion of serotonin (5-HT), and again after MB treatment. Bradykinin challenge failed to evoke a depressor response at baseline vascular tone but induced marked vasodilation after vascular tone was increased by 5-HT. Subsequent treatment with MB, however, failed to significantly diminish vasodilation to BK (p > 0.05). A second group of lobes (n = 4) was challenged with BK after cyclooxygenase inhibition and the doubling of vascular tone with serotonin infusion. The dose-dependent vasodilation to BK was diminished (p < 0.01) after treatment with 1.8 m M N<sup>ω</sup>-nitro- L-arginine (L-NA), a potent inhibitor of nitric oxide synthase. However, subsequent treatment with MB restored the vasodilator response to bradykinin to pre-L-NA values (p < 0.01). While our results suggest that vasodilation to bradykinin is mediated in part by NO formation, MB treatment does not appear to alter BK-induced vasodilation, and even enhanced vasodilation to bradykinin after L-NA. MB appears to have some nonspecific effects on vascular tone and reactivity that are unrelated to NO formation.

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          Author and article information

          J Vasc Res
          Journal of Vascular Research
          S. Karger AG
          24 September 2008
          : 33
          : 4
          : 340-345
          aDepartment of Surgery, University of Pennsylvania, Philadelphia, Pa., bDepartment of Physiology and Endocrinology, Medical College of Georgia, Augusta, Ga., USA
          159161 J Vasc Res 1996;33:340–345
          © 1996 S. Karger AG, Basel

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          Pages: 6
          Research Paper


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