Necessity of the Hypothalamic Paraventricular Nucleus for the Cardiovascular Responses to Activation of Bradykinin‐Sensitive Pericardial Afferents

Sympathetic drive is a major controller of cardiovascular function. While the arterial baroreceptors are known to regulate sympathetic drive to the cardiovascular system, other reflex mechanisms also play a role. The heart itself has an important sensory function via a variety of cardiac receptors that modulate cardiovascular responses by both neural and humoral reflexes. Bradykinin‐sensitive sympathetic afferent nerves from the heart can trigger marked increases in efferent sympathetic nerve activity to some cardiovascular target organs such as the kidney, arteries and veins. We reported previously that activation of the hypothalamic paraventricular nucleus (PVN) triggers an increase in arterial pressure, venous tone and cardiac output. This work tested the hypothesis that the PVN is necessary for the cardiovascular responses to activation of bradykinin‐sensitive pericardial afferents . 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 and venous blood pressures. The rats were placed in a stereotaxic frame and bilateral guide cannulae were implanted toward the PVN and cemented in place. A PE 10 catheter was placed in the pericardial space for the injection of bradykinin (BK; 1 μg/kg), an agent known to stimulate cardiac sympathetic afferents. The chest was closed and the rat allowed to breathe spontaneously. After recovery from these surgical interventions, the cardiovascular responses to pericardial injection of BK were recorded following PVN injection of vehicle or omega‐conotoxin (1 ng/nl; 200 nl), an N‐type calcium channel antagonist to impair neurotransmission in the PVN. Pericardial injection of BK following PVN injection of vehicle was associated with increases in mean arterial pressure (19±2 mm Hg) and heart rate (7±2 bpm). PVN injection of conotoxin did not markedly affect baseline arterial pressure or heart rate. However, after injection of conotoxin into the PVN, the pressor responses to pericardial injection of bradykinin were markedly attenuated (MAP: − 17±5 mm Hg; HR: −10±4 bpm). We interpret these data to indicate that neurotransmission in the PVN is required for the cardiovascular responses to activation of bradykinin‐sensitive pericardial afferents. Support or Funding Information Supported by NIH R01 HL136741‐02, the Sanford School of Medicine Medical Student Summer Research Program and the Basic Biomedical Sciences program of the Sanford School of Medicine. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .