Protective effect of relaxin in cardiac anaphylaxis: involvement of the nitric oxide pathway

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Abstract
Relaxin (RLX) is a multifunctional hormone best known for its role in pregnancy and parturition, that has been also shown to influence coronary perfusion and mast cell activation through the generation of endogenous nitric oxide (NO). In this study we report on the effects of RLX on the biochemical and mechanical changes of ex vivo perfused hearts isolated from ovalbumin‐sensitized guinea‐pigs induced by challenge with the specific antigen. The possible involvement of NO in the RLX action has been also investigated. A 30‐min perfusion with RLX (30 ng ml−1) before ovalbumin challenge fully abated the positive chronotropic and inotropic effects evoked by anaphylactic reaction to the antigen. RLX also blunted the short‐term coronary constriction following to antigen challenge. Conversely, perfusion with chemically inactivated RLX had no effect. The release of histamine in the perfusate and the accumulation of calcium in heart tissue induced by antigen challenge were significantly decreased by RLX, while the amounts of nitrites in the perfusate were significantly increased, as were NO synthase activity and expression and cGMP levels in heart tissue. These findings indicate that RLX has a protective effect in cardiac anaphylaxis which involves an up‐regulation of the NO biosynthetic pathway. British Journal of Pharmacology (2002) 137, 337–344. doi:10.1038/sj.bjp.0704879