Nitric Oxide Plays a Janus Role in the Pathogenesis of Tako-tsubo Cardiomyopathy

Introduction: Tako-tsubo cardiomyopathy (TTC) is fundamentally a catecholamine-stimulated myocardial inflammatory state, initiated by aberrant β2-adrenoceptor signalling in susceptible (usually female) myocardium. We have recently reported that (i) TTC patients exhibit evidence of “supranormal” NO signalling, (ii) at post-mortem, heart of patients dying of TTC have increased content of 3-nitrotyrosine (3NT), a marker of nitrosative stress. Furthermore, in a rat model of TTC, isoproterenol (ISOP) induces increased myocardial expression of both 3NT and thioredoxin-interacting protein (TXNIP), a pro-inflammatory protein normally suppressed by NO. We therefore sought to determine the effects of suppression of NO generation in this rat model. Methods: Female Sprague-Dawley rats, aged 4-5 months, were randomly assigned to one of two groups: ISOP (5mg/kg) (n = 11) and L-NAME (50mg/kg) + ISOP (n = 14). Echocardiography was performed at baseline and after 24 hours. Animals were then sacrificed and immunoblotting w...