Endothelial cells are exposed to a ubiquitous, yet unexamined electrical force caused by blood flow: the electrokinetic vascular streaming potential (EVSP). In this study, the hypothesis that extremely low frequency (ELF) electric fields parameterized by the EVSP have significant biological effects on endothelial cell properties was studied by measuring membrane potential and nitric oxide production under ELF stimulation between 0–2 Hz and 0–6.67 volts per meter. Using membrane potential and nitric oxide sensitive fluorescent dyes, bovine aortic endothelial cells (BAECs) in culture were studied in the presence and absence of EVSP-modeled electric fields. The transmembrane potential of BAECs was shown to depolarize between 1–7 mV with a strong dependency on both the magnitude and frequency of the isolated ELF field. The findings also support a field interaction with a frequency-dependent tuning curve. The ELF field complexly modulates the nitric oxide response to adenosine triphosphate stimulation with potentiation seen with up to a seven-fold increase. This potentiation was also frequency and magnitude dependent. An early logarithmic phase of NO production is enhanced in a field strength- dependent manner, but the ELF field does not modify a later exponential phase. This study shows that using electric fields on the order of those generated by blood flow influences the essential biology of endothelial cells. The inclusion of ELF electric fields in the paradigm of vascular biology may create novel opportunities for advancing both the understanding and therapies for treatment of vascular diseases.
The central nervous system plays an important role in essential hypertension in humans and in animal models of hypertension through modulation of sympathetic activity and Na and body fluid homeostasis. Data from animal models of hypertension suggest that the renin-angiotensin system in the subfornical organ (SFO) of the brain is critical for hypertension development. We recently reported that the brain (pro)renin receptor (PRR) is a novel component of the brain renin-angiotensin system and could be a key initiator of the pathogenesis of hypertension. Here, we examined the expression level and cellular distribution of PRR in the SFO of postmortem human brains to assess its association with the pathogenesis of human hypertension. Postmortem SFO tissues were collected from hypertensive and normotensive human subjects. Immunolabeling for the PRR and a retrospective analysis of clinical data were performed. We found that human PRR was prominently expressed in most neurons and microglia, but not in astrocytes, in the SFO. Importantly, PRR levels in the SFO were elevated in hypertensive subjects. Moreover, PRR immunoreactivity was significantly correlated with systolic blood pressure but not body weight, age, or diastolic blood pressure. Interestingly, this correlation was independent of antihypertensive drug therapy. Our data indicate that PRR in the SFO may be a key molecular player in the pathogenesis of human hypertension and, as such, could be an important focus of efforts to understand the neurogenic origin of hypertension. NEW & NOTEWORTHY This study provides evidence that, in the subfornical organ of the human brain, the (pro)renin receptor is expressed in neurons and microglia cells but not in astrocytes. More importantly, (pro)renin receptor immunoreactivity in the subfornical organ is increased in hypertensive humans and is significantly correlated with systolic blood pressure.
A 59-year-old bookkeeper presented with psychiatric symptoms in the context of stressors and past history of depression, for which her GP prescribed sertraline and olanzapine. Following a further deterioration in her mental state she was referred to acute psychiatric services, and there found to have dementia and myoclonus, and investigations supported a diagnosis of probable Creutzfeldt-Jakob disease, sporadic type (sCJD). This paper serves to outline the emerging literature challenging the notion that suggests psychiatric symptoms are uncommon in the presentation of sCJD.
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