Electric fields caused by blood flow modulate vascular endothelial electrophysiology and nitric oxide production

Abstract

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.

Current intensity‐ and polarity‐specific online and aftereffects of transcranial direct current stimulation: An fMRI study

“…If the observed effects are not completely accounted for by neurovascular coupling, potentially these effects could also be partially driven by direct effects of stimulation on blood vessels. Direct vessel dilation has been proposed as potential mechanism in previous studies given the possibility that low intensities of DC stimulation may exert direct effects on endothelial cells which can increase nitric oxide production (Trivedi, Hallock, & Bergethon, ). Both anodal and cathodal tDCS induced a relatively small increase in CBF during the online/stimulation block of the scan.…”

Direct Current Electric Field Stimulates Nitric Oxide Production and Promotes NO-Dependent Angiogenesis: Involvement of the PI3K/Akt Signaling Pathway

“…It should be noted that several other types of EF have an effect on NO production. For example, Trivedi et al [26] reported that an extremely-low-frequency EF, at the order of the fields generated by blood flow, enhanced the early logarithmic phase of NO production but did not enhance the subsequent exponential phase in endothelial cells. Petrofsky et al [27] showed that an EF of a biphasic sine wave stimulating the quadriceps muscle played a role in the NO-mediated blood flood response to electrical stimulation.…”

Electrical Stimulation Directs Migration, Enhances and Orients Cell Division and Upregulates the Chemokine Receptors CXCR4 and CXCR2 in Endothelial Cells

“…In a flow-independent model of dynamic angiogenesis in culture and in retinal vessels in vivo, endothelial cell cleavage was oriented orthogonal to the long axis of the vessel, which may promote vessel lengthening [47]. Interestingly, blood flow itself induces electrical signals called streaming potentials in microvessels, which at the endothelial cell surface are between 1 and 3 mV/mm [50]. Depending on the strength of the electric field, different responses were observed in endothelial cells.…”