METHYLENE-BLUE RESTORES VASODILATION TO BRADYKININ AFTER INHIBITION OF NITRIC-OXIDE PRODUCTION IN THE ISOLATED DOG LUNG

Methylene blue (MB) is a widely used putative inhibitor of nitric oxid e (NO)-dependent responses, particularly in cell culture and vascular ring studies. MB is postulated to diminish vasodilation to NO either b y preventing activation of guanylate cyclase by NO or by oxidizing NO formed by NO synthase. In the present study we examined whether MB inh ibited 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 ton e, after tone was doubled by infusion of serotonin (5-HT), and again a fter MB treatment. Bradykinin challenge failed to evoke a depressor re sponse at baseline vascular tone but induced marked vasodilation after vascular tone was increased by 5-HT. Subsequent treatment with MB, ho wever, failed to significantly diminish vasodilation to BK (p > 0.05). A second group of lobes (n = 4) was challenged with BK after cyclooxy genase inhibition and the doubling of vascular tone with serotonin inf usion. The dose-dependent vasodilation to BK was diminished (p < 0.01) after treatment with 1.8 mM N-omega-nitro-L-arginine (L-NA), a potent inhibitor of nitric oxide synthase. However, subsequent treatment wit h MB restored the vasodilator response to bradykinin to pre-L-NA value s (p < 0.01). While our results suggest that vasodilation to bradykini n is mediated in part by NO formation, MB treatment does not appear to alter BK-induced vasodilation, and even enhanced vasodilation to brad ykinin after LNA. MB appears to have some nonspecific effects on vascu lar tone and reactivity that are unrelated to NO formation.