Adrenergic C1 neurons monitor arterial blood pressure and determine the sympathetic response to hemorrhage

Abstract

Hemorrhage initially triggers a rise in sympathetic nerve activity (SNA) that maintains blood pressure (BP); however, SNA is suppressed following severe blood loss causing hypotension. We hypothesized that adrenergic C1 neurons in the rostral ventrolateral medulla (C1^RVLM) drive the increase in SNA during compensated hemorrhage, and a reduction in C1^RVLM contributes to hypotension during decompensated hemorrhage. Using fiber photometry, we demonstrate that C1^RVLM activity increases during compensated hemorrhage and falls at the onset of decompensated hemorrhage. Using optogenetics combined with direct recordings of SNA, we show that C1^RVLM activation mediates the rise in SNA and contributes to BP stability during compensated hemorrhage, whereas a suppression of C1^RVLM activity is associated with cardiovascular collapse during decompensated hemorrhage. Notably, re-activating C1^RVLM during decompensated hemorrhage restores BP to normal levels. In conclusion, C1 neurons are a nodal point for the sympathetic response to blood loss.

Keywords: GCaMP; RVLM; autonomic nervous system; blood pressure; calcium imaging; cardiovascular regulation; fiber photometry; optogenetics.