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Sympathoexcitation in ANG II-salt hypertension involves reduced SK channel function in the hypothalamic paraventricular nucleus.
Am J Physiol Heart Circ Physiol 2015; 308(12):H1547-55AJ

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+Show Affiliations

Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, Michigan;Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, Michigan; Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China; and.Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, Michigan;Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, Michigan;Department of Cardiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China; and.Department of Pharmaceutical Sciences, University of the Incarnate Word, Feik School of Pharmacy, San Antonio, Texas.Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, Michigan;Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, Michigan; qinghuic@mtu.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25862832

Citation

Larson, Robert A., et al. "Sympathoexcitation in ANG II-salt Hypertension Involves Reduced SK Channel Function in the Hypothalamic Paraventricular Nucleus." American Journal of Physiology. Heart and Circulatory Physiology, vol. 308, no. 12, 2015, pp. H1547-55.
Larson RA, Gui L, Huber MJ, et al. Sympathoexcitation in ANG II-salt hypertension involves reduced SK channel function in the hypothalamic paraventricular nucleus. Am J Physiol Heart Circ Physiol. 2015;308(12):H1547-55.
Larson, R. A., Gui, L., Huber, M. J., Chapp, A. D., Zhu, J., LaGrange, L. P., ... Chen, Q. H. (2015). Sympathoexcitation in ANG II-salt hypertension involves reduced SK channel function in the hypothalamic paraventricular nucleus. American Journal of Physiology. Heart and Circulatory Physiology, 308(12), pp. H1547-55. doi:10.1152/ajpheart.00832.2014.
Larson RA, et al. Sympathoexcitation in ANG II-salt Hypertension Involves Reduced SK Channel Function in the Hypothalamic Paraventricular Nucleus. Am J Physiol Heart Circ Physiol. 2015 Jun 15;308(12):H1547-55. PubMed PMID: 25862832.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sympathoexcitation in ANG II-salt hypertension involves reduced SK channel function in the hypothalamic paraventricular nucleus. AU - Larson,Robert A, AU - Gui,Le, AU - Huber,Michael J, AU - Chapp,Andrew D, AU - Zhu,Jianhua, AU - LaGrange,Lila P, AU - Shan,Zhiying, AU - Chen,Qing-Hui, Y1 - 2015/04/10/ PY - 2014/11/17/received PY - 2015/04/07/accepted PY - 2015/4/12/entrez PY - 2015/4/12/pubmed PY - 2015/9/22/medline KW - angiotensin II KW - hypertension KW - paraventricular nucleus KW - small-conductance Ca2+-activated K+ channels KW - sympathetic nerve activity SP - H1547 EP - 55 JF - American journal of physiology. Heart and circulatory physiology JO - Am. J. Physiol. Heart Circ. Physiol. VL - 308 IS - 12 N2 - 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. SN - 1522-1539 UR - https://www.unboundmedicine.com/medline/citation/25862832/Sympathoexcitation_in_ANG_II_salt_hypertension_involves_reduced_SK_channel_function_in_the_hypothalamic_paraventricular_nucleus_ L2 - http://www.physiology.org/doi/full/10.1152/ajpheart.00832.2014?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -