The neural control of arterial pressure by non‐catecholaminergic RVLM

Abstract

Tonic sympathetic nerve activity (SNA) is necessary for the maintenance of arterial pressure (AP) under anesthesia, and this tone is dependent on supraspinal input. Over the last two centuries, numerous studies have collectively identified the rostral ventrolateral medulla (RVLM) as a critical region for neural control of AP and SNA in anesthetized animals, however the relevance of these results to conscious animals and the nature of the RVLM neurons responsible remain conjectural. The RVLM has direct projections onto sympathetic preganglionic neurons, but the evidence that this is the critical pathway for AP regulation and SNA in conscious animals is not definitive—and even if this is the principal BP regulatory pathway of the RVLM, the bulbospinal neurons that produce these effects are still debated.Historically, the most prominent pressor candidate within the RVLM has been the rostral portion of the catecholaminergic C1 group. Rostral C1 neurons are glutamatergic, occupy a ventral region of the medulla that is coextensive with the vasomotor RVLM region, are barosensitive, directly innervate sympathetic preganglionic neurons, and activate sympathetic nerve discharge upon stimulation. Despite these data, optogenetic stimulation of C1 in conscious and anesthetized rodents has thus far failed to achieve the magnitude of increases in arterial pressure predicted by pharmacological stimulation of the RVLM.Here, we show that stimulation of a non‐catecholaminergic population within the RVLM is sufficient to increase AP in conscious mice, even after C1 lesion. We then targeted bulbospinal neurons using a retrograde virus and demonstrated that optogenetic activation of only bulbospinal RVLM neurons increases AP in conscious mice, and in anesthetized mice, stimulation increases AP and renal sympathetic nerve activity. Unlike optogenetic stimulation of C1 neurons, stimulation of non‐catecholaminergic bulbospinal RVLM causes robust and sustained increases in AP in both conscious and anesthetized states, and sustained increases in SNA under anesthesia. This data suggests non‐catecholaminergic bulbospinal neurons are powerful activators of AP and SNA and may play an important role along with C1 in arterial pressure maintenance.Support or Funding InformationAmerican Heart Association Predoctoral Fellowship; University of Virginia Wagner FellowshipThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.