title: Sympathoexcitation in ANG II-salt hypertension involves reduced SK channel function in the hypothalamic paraventricular nucleus.
abstract: Hypertension (HTN) resulting from subcutaneous infusion of ANG II and dietary high salt (HS) intake involves sympathoexcitation. Recently, we reported reduced small-conductance Ca(2+)-activated K(+) (SK) current and increased excitability of presympathetic neurons in the paraventricular nucleus (PVN) in ANG II-salt HTN. Here, we hypothesized that ANG II-salt HTN would be accompanied by altered PVN SK channel activity, which may contribute to sympathoexcitation in vivo. In anesthetized rats with normal salt (NS) intake, bilateral PVN microinjection of apamin (12.5 pmol/50 nl each), the SK channel blocker, remarkably elevated splanchnic sympathetic nerve activity (SSNA), renal sympathetic nerve activity (RSNA), and mean arterial pressure (MAP). In contrast, rats with ANG II-salt HTN demonstrated significantly attenuated SSNA, RSNA, and MAP (P < 0.05) responses to PVN-injected apamin compared with NS control rats. Next, we sought to examine the individual contributions of HS and subcutaneous infusion of ANG II on PVN SK channel function. SSNA, RSNA, and MAP responses to PVN-injected apamin in rats with HS alone were significantly attenuated compared with NS-fed rats. In contrast, sympathetic nerve activity responses to PVN-injected apamin in ANG II-treated rats were slightly attenuated with SSNA, demonstrating no statistical difference compared with NS-fed rats, whereas MAP responses to PVN-injected apamin were similar to NS-fed rats. Finally, Western blot analysis showed no statistical difference in SK1-SK3 expression in the PVN between NS and ANG II-salt HTN. We conclude that reduced SK channel function in the PVN is involved in the sympathoexcitation associated with ANG II-salt HTN. Dietary HS may play a dominant role in reducing SK channel function, thus contributing to sympathoexcitation in ANG II-salt HTN.
authors: Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, Michigan;
authors: Robert A
authors: RA
authors: Larson
authors: Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, Michigan; Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China; and.
authors: Le
authors: L
authors: Gui
authors: Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, Michigan;
authors: Michael J
authors: MJ
authors: Huber
authors: Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, Michigan;
authors: Andrew D
authors: AD
authors: Chapp
authors: Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China; and.
authors: Jianhua
authors: J
authors: Zhu
authors: Department of Pharmaceutical Sciences, University of the Incarnate Word, Feik School of Pharmacy, San Antonio, Texas.
authors: Lila P
authors: LP
authors: LaGrange
authors: Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, Michigan;
authors: Zhiying
authors: Z
authors: Shan
authors: Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, Michigan; qinghuic@mtu.edu.
authors: Qing-Hui
authors: QH
authors: Chen
mesh_terms: D000200:Action Potentials; D000804:Angiotensin II; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D015536:Down-Regulation; D006339:Heart Rate; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D007668:Kidney / Q000294:innervation*; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017673:Sodium Chloride, Dietary; D013153:Splanchnic Nerves / Q000503:physiopathology; D017779:Sympathetic Fibers, Postganglionic / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D026902:Potassium Channel Blockers; D051640:Small-Conductance Calcium-Activated Potassium Channels; D017673:Sodium Chloride, Dietary; D000804:Angiotensin II
keywords: angiotensin II; hypertension; paraventricular nucleus; small-conductance Ca2+-activated K+ channels; sympathetic nerve activity