Exercise augments small conductance Ca2+ -activated potassium channel (SK) function in the paraventricular nucleus (PVN) of Sprague Dawley rats to reduce sympathetic outflow

Abstract

Elevated sympathetic outflow is a key feature of cardiovascular disease (CVD) that worsens disease progression. Our lab has shown that SK channels expressed in the PVN play a crucial role in regulating neuronal activity and sympathetic outflow, and that SK channels become dysfunctional in rats fed a high salt diet. Exercise has been shown to be an effective treatment for reducing sympathoexcitation in CVD including hypertension and heart failure, but the underlying mechanisms are not fully understood. We hypothesized that aerobic exercise would upregulate SK channel function in the PVN to reduce sympathetic nerve activity (SNA). To test this, 5–6 week old Sprague Dawley rats were randomly divided into sedentary (SED) and exercise (EXT) two groups and fed a 0.4% NaCl normal salt diet. Following acclimation, EXT groups ran on a motorized treadmill 5 days/week for 8-10 weeks. Conscious blood pressure was measured weekly via tail plethysmography. After 8-10 weeks, animals were anesthetized and underwent in vivo surgery to record the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) following PVN microinjection of the SK channel blocker, apamin (0.25mM, 60nL/side). The data showed that the RSNA response to PVN apamin was significantly enhanced in EXT rats compared with SED rats (320.8 ± 174.6 % baseline, n=9 vs 184.8 ± 143.1 % baseline, n=9; p = 0.02). The corresponding ABP response to apamin was not significantly different in EXT rats compared with SED rats (20.40 ± 9.98 mmHg, n=9 vs 25.27 ± 9.97 mmHg, n=8; p = 0.1658). Our data indicates exercise enhances PVN SK channel function to reduce sympathetic outflow. This improvement of SK channel function may be one mechanism by which exercise reduces SNA in CVD including hypertension and heart failure. Support: 1R15HL145655 (Chen); 1R15 HL150703 (Shan); MTU Health Research Institute. 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.