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.
Journal article
2018-04-01T00:00:00+00:00
3
213 - 226
13
3AB, 3-aminobenzamide, ANOVA, analysis of variance, ISO, isoproterenol, LV, left ventricular, NFκB, nuclear factor kappa B, NO, nitric oxide, NOS, nitric oxide synthase, NT, nitrotyrosine, O2–, superoxide, ONOO–, peroxynitrite, PAR, poly(ADP-ribose), PARP, poly(ADP-ribose) polymerase, TS, Takotsubo syndrome, TXNIP, thioredoxin-interacting protein, Takotsubo cardiomyopathy, myocardial inflammation, oxidative stress, poly(ADP-ribose) polymerase-1