Enhanced NO Signaling in Patients with Takotsubo Cardiomyopathy: Short-Term Pain, Long-Term Gain?

Abstract

TTC is associated with intensification of NO signaling relative to that in normal age-matched females. Our data are consistent with this intensified signal's potential contribution to the extent of initial myocardial injury, but conversely to accelerated recovery.

International Expert Consensus Document on Takotsubo Syndrome (Part I): Clinical Characteristics, Diagnostic Criteria, and Pathophysiology

“… 106–108 Since the β 2 -adrenoceptor is linked via G i activation to stimulation of endothelial nitric oxide (NO) synthase, it seems possible, that peroxynitrate mediated nitrosative stress could lead to negative inotropy and inflammation in TTS. Indeed, TTS patients have markers of increased NO signalling 109 and post-mortem hearts of TTS patients also demonstrate markers of increased nitrosative stress. 110 Peroxynitrite release would also result in activation of poly(ADP-ribose)-transferase-1, which might contribute to the myocardial energetic impairment, which has recently been reported in patients with TTS.…”

Nitrosative Stress as a Modulator of Inflammatory Change in a Model of Takotsubo Syndrome

“…We made a series of observations which suggest that nitrosative stress may be critical to both inflammation and energetic impairment in TS. We showed that patients with TS differ from age-matched female control subjects with regard to 2 aspects of nitric oxide (NO) signaling (16) . Specifically, patients with TS exhibited greater platelet responsiveness to the antiaggregatory effects of NO.…”

Evidence of nitrosative stress within hearts of patients dying of Tako-tsubo cardiomyopathy

“…Paur et al [5] have recently demonstrated that TTC-like changes in left ventricular wall motion in a rat model following injection of epinephrine reflected primarily consequences of increased β 2 -adrenoceptor signalling in a rat model. However, to date, no studies have evaluated mechanisms of the inflammatory activation which represents the principal mechanism of left ventricular systolic dysfunction.We have recently documented that patients with TTC exhibit 'supranormal' nitric oxide (NO) signalling compared to controls, including unusually low plasma concentrations of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine and increased anti-aggregatory responses to the NO donor sodium nitroprusside [6]. Combined with evidence that β 2 -adrenoceptors are coupled to NOS [7], these findings led us to evaluate whether peroxynitrite (ONOO − ) generation might be a central component of inflammatory activation in TTC.…”

“…We have recently documented that patients with TTC exhibit 'supranormal' nitric oxide (NO) signalling compared to controls, including unusually low plasma concentrations of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine and increased anti-aggregatory responses to the NO donor sodium nitroprusside [6]. Combined with evidence that β 2 -adrenoceptors are coupled to NOS [7], these findings led us to evaluate whether peroxynitrite (ONOO − ) generation might be a central component of inflammatory activation in TTC.…”