PVN SK channel blockade alters sympathetic nerve bursting pattern in angiotensin II-infused rats
Authors: Disser Jenna , Chen Qing-Hui , Larson Robert 
Published: May 2023

Sympathetic nerve activity (SNA) is known to demonstrate rhythmic activity that is synchronized with the respiratory and the cardiac cycles. These oscillations arise through integration of signals from lung inflation afferents, baroreceptor afferents, and respiratory neurons in the brainstem that influence presympathetic neurons in the rostral ventrolateral medulla (RVLM). The hypothalamic paraventricular nucleus (PVN) is a prominent regulatory center for sympathetic nerve activity (SNA) and PVN neurons have axon projections to the RVLM. Blockade of small conductance calcium-activated potassium (SK) channels in the PVN significantly increases splanchnic and renal SNA and dysfunction of SK channels contributes to the pathogenesis of hypertension. The aim of this study was to determine the influence of chronic AngII infusion on SNA firing patterns at rest and following PVN SK channel blockade with apamin. All experiments were performed in ventilated, anesthetized (urethane 800mg/kg & α-chloralose 80mg/kg) male Sprague-Dawley control (Ctrl; n=5) rats, or rats infused with AngII (150 ng·kg−1·min−1) for 2 weeks (n=4). Bilateral PVN microinjection of the SK channel blocker apamin (12.5pmol, 50μL) significantly (p<0.05) increased splanchnic SNA (Ctrl Δ253±61 vs. AngII Δ166±72%) and mean arterial pressure (MAP; CtrlΔ28.7±7.6 vs. AngII Δ34.5±3mmHg) to a similar extent from baseline in Ctrl and AngII rats whereas renal SNA (Ctrl Δ216±48 vs. AngII Δ97±22%; p<0.05) responses were significantly attenuated in AngII infused rats. Power spectral density was calculated on 5-minute segments of SNA during baseline, and during the maximum response to apamin. Data were normalized and expressed as a percentage of total power from 0-15Hz. Splanchnic and renal SNA spectral power in the 0-2Hz (low) frequency band was similar between Ctrl and AngII rats at baseline. PVN microinjection of apamin significantly (p<0.05) increased spectral power in the 0-2Hz frequency band similarly in both groups. In contrast, baseline spectral power in the 5-7Hz (cardiac) frequency band was significantly higher in AngII rats compared to control for both splanchnic (Ctrl 10.4±2.3 vs. AngII 26.8±2.8%; p<0.05) and renal (Ctrl 19.9±3.8 vs. AngII 35.3±1.5%; p<0.05) SNA. Interestingly, PVN microinjection of apamin significantly (p<0.05) attenuated spectral power in the 5-7Hz frequency band in the AngII group alone for splanchnic (Ctrl 9.3±2.8 vs. AngII 7.7±0.8%) and renal (Ctrl 12.3±4.7 vs. AngII 11.1±1.9%) SNA. In conclusion, cardiac-related spectral power was significantly greater in AngII rats at baseline compared to Ctrl likely reflecting increased input from baroreceptor afferents. PVN SK channel blockade shifts the SNA burst pattern in both Ctrl and AngII rats towards lower frequencies bursts known to have a greater influence on vascular tone.

Funding: Michigan Technological University (Larson); NIH 1R15HL145655(Chen)

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.