Nitric Oxide Synthase 1 Adaptor Protein Dysfunction in the Nucleus Tractus Solitarii Contributes to the Neurogenic Cardiac Damage and QT Interval Prolongation

TL;DRAbstract

Variants of the Nitric Oxide Synthase 1 Adaptor Protein (NOS1AP) locus are strongly related to QT interval prolongation and sudden cardiac death (SCD) in human. Neurogenic cardiac damage due to subarachnoid hemorrhage, stroke, epilepsy and myocardial infarction is known to contribute to sudden death in most cases. Our aim was to study the role of NOS1AP in the neurogenic cardiac damage by silencing NOS1AP expression in the Nucleus Tractus Solitarii (NTS) area of the brainstem using lentiviral vector-mediated NOS1AP shRNA (Lv-NOS1AP-shRNA). Real time PCR data showed NOS1AP mRNA levels were expressed in the NTS 3-fold higher than other organs such as kidney and heart in Sprague Dawley (SD) rats. Microinjection of Lv-NOS1AP-shRNA in the NTS caused significant reduction in NOS1AP expression in SD rats. NOS1AP knockdown in NTS did not alter blood pressure (BP), heart rate (HR) recorded by radiotelemetry. However, ECG analysis revealed heart rate variability (HRV) was significantly reduced (

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