Premium
Modulation of the pharmacological actions of nitrovasodilators by methylene blue and pyocyanin
Author(s) -
Gryglewski R.J.,
Zembowicz A.,
Salvemini D.,
Taylor G.W.,
Vane J.R.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb14422.x
Subject(s) - chemistry , methylene blue , sodium nitroprusside , potency , snap , nitric oxide , endothelium derived relaxing factor , aorta , in vitro , pharmacology , stereochemistry , biochemistry , medicine , photocatalysis , computer science , catalysis , computer graphics (images) , organic chemistry
1 In superfused precontracted strips of rabbit aorta, methylene blue (MeB) or pyocyanin (Pyo, 1‐hydroxy‐5‐methyl phenazinum betaine) at concentrations of 1–10 μ m inhibited relaxations induced by endothelium‐derived relaxing factor (EDRF), glyceryl trinitrate (GTN), S‐nitroso‐N‐acetyl‐penicillamine (SNAP) or 3‐morpholino‐sydnonimine (SIN‐1). However, the vasorelaxant actions of sodium nitroprusside (NaNP) or sodium nitrite (NaNO 2 ) were enhanced by MeB or Pyo. Oxyhaemoglobin (HbO 2 , 1 μ m ) inhibited the activities of EDRF and all of the nitrovasodilators studied. Vascular preparations were not relaxed by Pyo unless pretreated with NaNP (0.05–10 μ m ). 2 In bathed, precontracted rings of rabbit aorta, Pyo (10 μ m ) produced a shift to the left of the cumulative concentration‐response curve for NaNP (0.01–10 μ m ). The rise in guanosine‐3′:5′‐cyclic monophosphate (cyclic GMP) content of aortic tissue was also enhanced. 3 The vasorelaxant potency of NaNP (30 μ m ) at pH 5–8 and at 37°C remained unchanged over 2.5 h while a solution of SNAP (30 μ m ) progressively lost its biological activity over 60 min. The in vitro degradation of the biological activity of SNAP was accelerated by MeB (150 μ m ) or Pyo (150 μ m ), whereas the vasorelaxant potency NaNP (30 μ m ) was doubled when incubated with MeB or Pyo. 4 In human platelet‐rich plasma, MeB or Pyo (0.3–3.0 μ m ) uncovered an anti‐aggregatory action of subthreshold concentrations of NaNP (4–8 μ m ). This was abrogated by HbO 2 (10 μ m ). In contrast to NaNP the anti‐aggregatory effect of SNAP (2–20 μ m ) was antagonized by MeB (10 μ m ), Pyo (10 μ m ) or HbO 2 (10 μ m ). 5 We conclude that MeB or Pyo differ from HbO 2 in their mode of interaction with nitrovasodilators. HbO 2 scavenges nitric oxide that is released from all types of nitrovasodilators. MeB and Pyo exert a similar action towards organic nitrovasodilators (e.g. SNAP, SIN‐1). However, the pharmacological actions of inorganic nitrovasodilators (e.g. NaNP or NaNO 2 ) are potentiated by MeB and Pyo owing to facilitation of the intracellular release of nitric oxide from the inorganic nitrovasodilators.