In-vivo correlations between skin metabolic oscillations and vasomotion in wild-type mice and in a model of oxidative stress

Abstract

Arterioles in the cutaneous microcirculation frequently display an oscillatory phenomenon defined vasomotion, consistent with periodic diameter variations in the micro-vessels associated with particular physiological or abnormal conditions. The cellular mechanisms underlying vasomotion and its physiological role have not been completely elucidated. Various mechanisms were demonstrated, based on cell Ca2+ oscillations determined by the activity of channels in the plasma membrane or sarcoplasmic reticulum of vascular cells. However, the possible engagement in vasomotion of cell metabolic oscillations of mitochondrial or glycolytic origin has been poorly explored. Metabolic oscillations associated with the production of ATP energy were previously described in cells, while limited studies have investigated these fluctuations in-vivo. Here, we characterised a low-frequency metabolic oscillator (MO-1) in skin from live wild-type and Nrf2−/− mice, by combination of fluorescence spectroscopy and wavelet transform processing technique. Furthermore, the relationships between metabolic and microvascular oscillators were examined during phenylephrine-induced vasoconstriction. We found a significant interaction between MO-1 and the endothelial EDHF vasomotor mechanism that was reduced in the presence of oxidative stress (Nrf2−/− mice). Our findings suggest indirectly that metabolic oscillations may be involved in the mechanisms underlying endothelium-mediated skin vasomotion, which might be altered in the presence of metabolic disturbance.

Low‐frequency oscillations of murine skin microcirculations and periodic changes of [Ca2+]i and [NO]i levels in murine endotheliocytes: An effect of provocative tests

“…It is possible that synchronized [Ca 2+ ] i oscillations in endothelial cells play the role of a negative regulator of endothelial SBP oscillations. A positive relationship between endothelial SBP oscillations and NAD(P)H level oscillations in 0.005–0.0072 Hz was described in rats (Smirni et al, 2019). The correlation between oscillations of cytoplasmic NAD(P)H level and [Ca 2+ ] i in individual cells of murine pancreas was shown (Voronina et al, 2002).…”

“…These intervals correspond to endothelial and myogenic intervals of SBP oscillations determined for humans [Söderström et al, 2003), rats (Newman et al, 2009; Stauss et al, 1999; Wei et al, 2021), and mice (M. E. Astashev et al, 2019). The peaks of [Ca 2+ ] i and [NO] i oscillations are localized in interval 0.005–0.01 Hz, which correspond to NO‐independent endothelial interval (Kvernmo et al, 1999; Smirni et al, 2019]. The oscillations of [Ca 2+ ] i with the frequency of ∼0.01 Hz and lower described in the literature for human umbilical vein endothelial cells (HUVECs), endothelial cells from the human aorta, and embryonic endothelial cells of Danio rerio (Jacob, 1991; Yokota et al, 2015; Zhu et al, 2008).…”

A novel MRI analysis for assessment of microvascular vasomodulation in low-perfusion skeletal muscle

“…A final comment pertains to the study of microvascular dynamics. There is ample literature on the oscillatory nature of microvascular blood flow, with the majority employing optical perfusion methods with a very high temporal sampling rate 16,17 . With such rapid sampling, one can observe a wide frequency range associated with cardiac, respiratory, or myogenic origins.…”

Sural Nerve Perfusion in Mice

“…In peripheral nerves microvascular innervation and local endothelial signaling play an important role in maintaining the vascular tone (Zochodne, 2018) and power spectral density analysis of RBCv signal indicates that both mechanisms might be at play in the microvasculature of the sural nerve (Figure 4). Power spectral density analysis showed that RBCv oscillations between 0.02 and 0.05 Hz, potentially corresponding to neurogenic regulation (Smirni et al, 2019), were reduced at 32 • C compared to 28 • C. Oscillations at the very low frequencies (0-0.02 Hz), potentially corresponding to the endothelial involvement and nitric oxide release (Stefanovska et al, 1999;Smirni et al, 2019), appeared more pronounced at 32 • C and 37 • C than at 28 • C but were not statistically different, however, were significantly increased by increasing MAP. Even though the relatively short recoding lengths of 30 s limit the strength of conclusions that can be derived from the changes in oscillations in RBCv signal, the analysis shows that local blood flow control in the nerve is affected by changing temperatures and by MAP.…”

“…To determine whether our RBCv measurements were sufficiently sensitive to detect subtle oscillations in blood flow across different timescales (Stefanovska et al, 1999;Smirni et al, 2019), we subjected RBCv time series to power spectrum analysis using Matlab's Welch's power spectral density estimation function. Such oscillations are observed in peripheral vessels in mice and humans and they have been ascribed to specific cellular and physiological sources according to their characteristic frequency ranges (Stefanovska et al, 1999;Smirni et al, 2019). Based on the literature, we pre-defined frequency bands to include oscillations characteristic to their sources: 0-0.02 Hz (endothelial), 0.02-0.05 Hz (neurogenic), 0.05-0.15 Hz (myogenic), 0.15-3 Hz (respiration), and 3-10 Hz (heart rate).…”