Novel sensory pathway from bone marrow to ventrolateral periaqueductal gray regulates blood pressure in the hypertensive rat

Introduction: A range of pathophysiological conditions present with dysfunctional immune and autonomic nervous system (ANS), including hypertension. Here, we present new data from a hypertensive rodent model that demonstrate an altered afferent communication between the bone marrow (BM), a major hematopoietic organ, and midbrain autonomic regions that regulate blood pressure. Considering that BM is pro-inflammatory in hypertension, we propose a dysfunctional BM-brain communication will be present in hypertensive rodents. Methods: Male adult (12-14wo) spontaneously hypertensive rats (SHR) and their age-matched normotensive controls, the Wistar-Kyoto (WKY) rats, were used in this study. Rats were anesthetized with isoflurane (1.5%) and mean arterial pressure (MAP) and heart rate (HR) were monitored in real time via a femoral arterial catheter and ECG leads in Spike2 (CED UK). Electrical stimulation (100 square pulses, 20Hz; 5mA, 500us) was applied inside the femoral bone cavity for stimulation of BM afferents, before and after a unilateral bicuculline (BIC) microinjection (100nl, 0.4mM) in the dorsolateral, lateral, or ventrolateral periaqueductal gray (PAG) separately. Results: Electrical BM stimulation produced an immediate stimulation-dependent decrease in MAP and HR that was of similar amplitude in the WKY versus SHR (WKY, from baseline: ΔMAP=-8±1mmHg, ΔHR=-1± 4bpm; SHR, from baseline: ΔMAP=-9±2mmHg, ΔHR=-6±4bpm; P=0.5 ANOVA). However, these responses were significantly enhanced in the SHR, but not the WKY, immediately following an injection of BIC in the ventrolateral PAG (vlPAG; WKY, from baseline: ΔMAP=-9±1mmHg; SHR, from baseline: ΔMAP=-31±3mmHg; ****P<0.0001 ANOVA). Conclusion: We demonstrate a novel BM-vlPAG afferent neural pathway in regulation of blood pressure. This neuronal circuitry may be dampened in hypertension due to elevated GABA signaling in the vlPAG.

1) University of Kent Deputy Vice-Chancellor's Partnership Fund to SK and JZ; 2) The Physiological Society UK to SK; 3) NIH R01 HL152162 to JZ

This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.