Activation of Bradykinin‐Sensitive Pericardial Afferents Increases Splanchnic Nerve Activity

Sympathetic drive plays a key role in control of cardiovascular function. The heart performs an important sensory function via a variety of cardiac receptors that modulate sympathetic drive. Bradykinin‐sensitive sympathetic afferent nerves from the heart can trigger marked increases in efferent sympathetic nerve activity to some cardiovascular targets such as the kidney. We reported previously that pericardial injection of bradykinin increased venous tone and cardiac output. The splanchnic vascular compartment plays an important role in control of venous return and cardiac output. This work tested the hypothesis that activation of bradykinin‐sensitive pericardial afferents increases postganglionic splanchnic sympathetic nerve activity. Sprague Dawley rats were anesthetized with a cocktail of alpha chloralose (80 mg/kg) and urethane (800 mg/kg). Catheters were placed in the femoral artery and vein to record arterial pressure (MAP) and heart rate (HR). A PE10 catheter was placed in the pericardial space for the injection of bradykinin (BK), an agent known to stimulate cardiac sympathetic afferents. The chest was closed and the rat allowed to breathe spontaneously. The splanchnic sympathetic nerve was isolated via a dorsal approach and placed on recording electrodes. After stabilization, the blood pressure, heart rate, and integrated splanchnic nerve activity (SPLNA) responses to pericardial injection of BK or vehicle were recorded. Responses were also recorded for intravenous injection of dimethylphenylpiperazinium (DMPP 150 ug/kg), a ganglionic stimulant, and a ganglion blocker (hexamethonium 20 mg/kg). Pericardial injection of saline vehicle had little effect (MAP: 0.1±0.4 mm Hg; HR: 1.2±1.4 bpm; SPLNA 1±2%). In contrast, intravenous injection of a ganglionic stimulant, DMPP, increased MAP (23±1 mm Hg) and SPLNA (95±46%). Pericardial injection of BK (10 ug/kg) increased MAP (21±3 mm Hg), HR (28±7 bpm) and SPLNA (93±37%). Ganglionic blockade with hexamethonium reduced SPLNA (−75±6%) and abolished the responses to pericardial injection of BK (MAP: −1±3 mm Hg; HR: −2±1 bpm; SPLNA: 7±30 %). We interpret these data to indicate that activation of bradykinin‐sensitive pericardial afferents increases postganglionic splanchnic sympathetic nerve activity. This finding is consistent with the view that activation of the cardiac sympathetic afferent reflex elicits a venoconstrictor response to increase venous return from the splanchnic vascular compartment. Support or Funding Information Supported by NIH R01 HL136741‐03 (DM), R01 DK114663‐1 (HZ), and the Basic Biomedical Sciences program of the Sanford School of Medicine, University of South Dakota.