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EFFECT OF EXERCISE ON HYPOTHALAMIC PARAVENTRICULAR NUCLEUS SK CHANNEL FUNCTION IN NORMAL AND HIGH SALT CONDITIONS
Date of Award
Campus Access Master's Thesis
Master of Science in Kinesiology (MS)
Administrative Home Department
Department of Kinesiology and Integrative Physiology
Committee Member 1
Committee Member 2
Committee Member 3
Increased sympathetic outflow is a hallmark of cardiovascular disease (CVD) (Grassi, Seravalle et al. 2015). Previously, our lab demonstrated that small conductance Ca2+ activated K+ channels (SK) expressed in the paraventricular nucleus of the hypothalamus (PVN) play a crucial role in regulating neuronal firing rate and sympathetic outflow in rats with AngII-salt hypertension (Larson, Gui et al. 2015). Therefore, antihypertensive therapies targeted at upregulating SK channel function in the PVN should be pursued. Exercise is a powerful intervention to treat CVD. However, little is known about the interaction between SK channels in the PVN and exercise. Initially, we showed that following an 8-week exercise protocol, normotensive Sprague Dawley (SD) rats exhibited an augmented change in renal sympathetic nerve activity (ΔRSNA) to PVN microinjection of apamin, an SK channel blocker. This trend warranted further investigation and prompted us to split 5–6-week-old SD rats into four groups including SD SED-NS, SD EXT-NS, SD SED-HS, and SD EXT-HS. DAHL rats, a model of salt sensitive hypertension, were also split into EXT-HS and SED-HS groups. HS groups were fed 4% NaCl food while NS groups ate 0.4% NaCl chow. 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 ΔRSNA and ΔMAP following PVN apamin microinjection. We found that exercise training significantly upregulated SK channel function in the PVN of normotensive SD rats fed a NS diet compared to SED rats (320.8 ± 174.6 % baseline, n=9 vs 184.8 ± 143.1 % baseline, n=9; p = 0.02) but had little effect on the blood pressure response to apamin (20.40 ± 9.98 mmHg, n=9 vs 25.27 ± 9.97 mmHg, n=8; p = 0.1658). In SD HS and DAHL rats, we did not see significant differences in ΔRSNA and ΔMAP between SED and EXT groups. Small sample size and mixed sexes possibly contributed to this lack of positive results.
Collectively, these results indicate exercise can enhance PVN SK channel function to reduce sympathetic outflow. This improvement of SK channel function may be one mechanism by which exercise protects against the development of salt sensitive hypertension.
Miodonski, Gregory J., "EFFECT OF EXERCISE ON HYPOTHALAMIC PARAVENTRICULAR NUCLEUS SK CHANNEL FUNCTION IN NORMAL AND HIGH SALT CONDITIONS", Campus Access Master's Thesis, Michigan Technological University, 2022.