title: Methylene blue restores vasodilation to bradykinin after inhibition of nitric oxide production in the isolated dog lung.
abstract: 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 mM N omega-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.
authors.affiliation: Department of Surgery, University of Pennsylvania, Philadelphia, USA.
authors.forename: M B
authors.initials: MB
authors.lastname: Shapiro
authors.forename: J
authors.initials: J
authors.lastname: Endredi
authors.forename: I C
authors.initials: IC
authors.lastname: Ehrhart
authors.forename: W F
authors.initials: WF
authors.lastname: Hofman
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology*; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D008168:Lung / Q000098:blood supply*; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine; D012701:Serotonin / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D004791:Enzyme Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D012701:Serotonin; D001120:Arginine; D019001:Nitric Oxide Synthase; D001920:Bradykinin; D008751:Methylene Blue