Nitric oxide modulates cardiac and mast cell anaphylaxis

Area of Science:

• Cardiovascular Pharmacology
• Immunopharmacology
• Nitric Oxide Biology

Background:

• Anaphylaxis involves complex mediator release affecting cardiac function.
• Nitrite (NO2-), an oxidation product of nitric oxide (NO), is released during anaphylaxis.
• The role of endogenous and exogenous NO in cardiac anaphylaxis requires further elucidation.

Purpose of the Study:

• To investigate the role of nitric oxide (NO) in modulating cardiac anaphylaxis in an isolated guinea-pig heart model.
• To determine the effects of NO modulation on histamine release, coronary flow, and antigen-induced arrhythmias.

Main Methods:

• Utilized an isolated guinea-pig heart model subjected to anaphylaxis.
• Administered NG-monomethyl-L-arginine (MeArg) to inhibit NO synthesis and Sodium nitroprusside (NaNP) as an NO donor.
• Measured coronary flow, antigen-induced arrhythmias, and histamine and nitrite release.
• Investigated effects on isolated mast cells.

Main Results:

• Inhibition of NO synthesis (MeArg) worsened cardiac anaphylaxis, decreasing coronary flow, prolonging arrhythmias, and increasing histamine release while decreasing nitrite release.
• NO administration (NaNP) ameliorated cardiac anaphylaxis, increasing coronary flow, shortening arrhythmias, and decreasing histamine release while increasing nitrite release.
• MeArg enhanced and NaNP reduced antigen-induced histamine release from isolated mast cells.

Conclusions:

• Endogenous and exogenous NO antagonize vasoconstrictor mediators released during anaphylaxis.
• Nitric oxide plays a protective role in vitro cardiac anaphylactic reactions.
• Modulation of NO pathways represents a potential therapeutic strategy for anaphylaxis.