Search

Visual Abstract, Highlights • Treatment of female rats with a single dose of isoproterenol results in apical hypokinesis mimicking Takotsubo syndrome • Myocardial inflammation includes increased content of 3-nitrotyrosine and poly(ADP-ribose), indicating nitrosative stress and PARP-1 activation, respectively • Pretreatment with 3-aminobenzamide (a PARP-1 inhibitor) attenuates negative inotropic changes • We conclude that the peroxynitrite/PARP-1 cascade contributed to negative inotropy in this model of Takotsubo syndrome, consistent with the limited data available in patients, Summary Previous studies have shown that patients with Takotsubo syndrome (TS) have supranormal nitric oxide signaling, and post-mortem studies of TS heart samples revealed nitrosative stress. Therefore, we first showed in a female rat model that isoproterenol induces TS-like echocardiographic changes, evidence of nitrosative stress, and consequent activation of the energy-depleting enzyme poly(ADP-ribose) polymerase-1. We subsequently showed that pre-treatment with an inhibitor of poly(ADP-ribose) polymerase-1 ameliorated contractile abnormalities. These findings thus add to previous reports of aberrant β-adrenoceptor signaling (coupled with nitric oxide synthase activation) to elucidate mechanisms of impaired cardiac function in TS and point to potential methods of treatment.