Low-frequency oscillations of murine skin microcirculations and periodic changes of [Ca ] and [NO] levels in murine endotheliocytes: An effect of provocative tests.

The five frequency intervals of skin blood oscillation were described: cardiac, respiratory, myogenic, neurogenic, and endothelial. The endothelial interval is derived into NO-independent and NO-dependent. The exact molecular, cell, or systemic mechanisms of endothelial oscillations generation are unclear. We proposed that oscillations of Ca and NO in endotheliocytes may be possible sources of skin blood perfusion (SBP) oscillations in endothelial interval. To examine our hypothesis we compared the oscillations of cytoplasmic Ca and NO ([Ca ] and [NO] ) concentration in cultured murine microvascular endotheliocytes and SBP oscillations in mice. Local heating test and model hypoxia were used as tools to evaluate an interconnection of studied parameters. [Ca ] and [NO] were measured simultaneously by Fura-2 AM and DAF-FM. The SBP was measured by laser Doppler flowmetry. The [Ca ] and [NO] oscillations at 0.005-0.01 Hz were observed in endotheliocytes, that coincides the ranges of NO-independent endothelial interval. Heating decreased amplitude of [Ca ] and [NO] oscillations in cells in NO-independent endothelial interval, while amplitudes of SBP oscillations increased in NO-independent and NO-dependent intervals. Hypoxia reduced the [NO] oscillations amplitude. Heating test during hypoxia increased NO-independent endothelial SBP oscillations and decreased myogenic ones, did not effect on [NO] oscillations, and shifted [Ca ] oscillations peak from 0.005-0.01 Hz to 0.01-0.018 Hz. We observed the [Ca ] and [NO] oscillations synchronization within a cell and between cells for the first time. Heating abolished these synchronizations. Therefore low-frequency [Ca ] and [NO] oscillations in endotheliocytes may be considered as modulators of low-frequency endothelial SBP oscillations.