Young-Beom Kim1, Yoon Sik Kim, Woong Bin Kim, Feng-Yan Shen, Seung Won Lee, Hyun Joo Chung, Jeong Sook Kim, Hee Chul Han, Christopher S Colwell, Yang In Kim. 1. From the Department of Physiology (Y.-B.K., Y.S.K., W.B.K., F.-Y.S., S.W.L., H.J.C., H.C.H., Y.I.K.), and Neuroscience Research Institute (Y.-B.K., Y.S.K., W.B.K., F.-Y.S., S.W.L., H.J.C., H.C.H., Y.I.K.), Korea University College of Medicine, Seoul, Republic of Korea; Department of Physiology, Biomedical Science Institute and Brain Korea 21 Project Center, Kyung Hee University School of Medicine, Seoul, Republic of Korea (J.S.K.); and Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, CA (C.S.C.).
Abstract
RATIONALE: Increased arginine-vasopressin (AVP) secretion is a key physiological response to hyperosmotic stress and may be part of the mechanism by which high-salt diets induce or exacerbate hypertension. OBJECTIVE: Using deoxycorticosterone acetate-salt hypertension model rats, we sought to test the hypothesis that changes in GABA(A) receptor-mediated inhibition in AVP-secreting magnocellular neurons contribute to the generation of Na(+)-dependent hypertension. METHODS AND RESULTS: In vitro gramicidin-perforated recordings in the paraventricular and supraoptic nuclei revealed that the GABAergic inhibition in AVP-secreting neurons was converted into excitation in this model, because of the depolarization of GABA equilibrium potential. Meanwhile, in vivo extracellular recordings in the supraoptic nuclei showed that the GABAergic baroreflexive inhibition of magnocellular neurons was transformed to excitation, so that baroreceptor activation may increase AVP release. The depolarizing GABA equilibrium potential shift in AVP-secreting neurons occurred progressively over weeks of deoxycorticosterone acetate-salt treatment along with gradual increases in plasma AVP and blood pressure. Furthermore, the shift was associated with changes in chloride transporter expression and partially reversed by bumetanide (Na(+)-K(+)-2Cl(-) cotransporter inhibitor). Intracerebroventricular bumetanide administration during deoxycorticosterone acetate-salt treatment hindered the development of hypertension and rise in plasma AVP level. Muscimol (GABA(A) agonist) microinjection into the supraoptic nuclei in hypertensive rats increased blood pressure, which was prevented by previous intravenous V1a AVP antagonist injection. CONCLUSIONS: We conclude that the inhibitory-to-excitatory switch of GABAA receptor-mediated transmission in AVP neurons contributes to the generation of Na(+)-dependent hypertension by increasing AVP release. We speculate that normalizing the GABA equilibrium potential may have some utility in treating Na(+)-dependent hypertension.
RATIONALE: Increased arginine-vasopressin (AVP) secretion is a key physiological response to hyperosmotic stress and may be part of the mechanism by which high-salt diets induce or exacerbate hypertension. OBJECTIVE: Using deoxycorticosterone acetate-salthypertension model rats, we sought to test the hypothesis that changes in GABA(A) receptor-mediated inhibition in AVP-secreting magnocellular neurons contribute to the generation of Na(+)-dependent hypertension. METHODS AND RESULTS: In vitro gramicidin-perforated recordings in the paraventricular and supraoptic nuclei revealed that the GABAergic inhibition in AVP-secreting neurons was converted into excitation in this model, because of the depolarization of GABA equilibrium potential. Meanwhile, in vivo extracellular recordings in the supraoptic nuclei showed that the GABAergic baroreflexive inhibition of magnocellular neurons was transformed to excitation, so that baroreceptor activation may increase AVP release. The depolarizing GABA equilibrium potential shift in AVP-secreting neurons occurred progressively over weeks of deoxycorticosterone acetate-salt treatment along with gradual increases in plasma AVP and blood pressure. Furthermore, the shift was associated with changes in chloride transporter expression and partially reversed by bumetanide (Na(+)-K(+)-2Cl(-) cotransporter inhibitor). Intracerebroventricular bumetanide administration during deoxycorticosterone acetate-salt treatment hindered the development of hypertension and rise in plasma AVP level. Muscimol (GABA(A) agonist) microinjection into the supraoptic nuclei in hypertensiverats increased blood pressure, which was prevented by previous intravenous V1a AVP antagonist injection. CONCLUSIONS: We conclude that the inhibitory-to-excitatory switch of GABAA receptor-mediated transmission in AVP neurons contributes to the generation of Na(+)-dependent hypertension by increasing AVP release. We speculate that normalizing the GABA equilibrium potential may have some utility in treating Na(+)-dependent hypertension.
Authors: Kirthikaa Balapattabi; George E Farmer; Blayne A Knapp; Joel T Little; Martha Bachelor; Joseph P Yuan; J Thomas Cunningham Journal: J Neuroendocrinol Date: 2019-06-14 Impact factor: 3.627
Authors: Jeremy A Sandgren; Danny W Linggonegoro; Shao Yang Zhang; Sarah A Sapouckey; Kristin E Claflin; Nicole A Pearson; Mariah R Leidinger; Gary L Pierce; Mark K Santillan; Katherine N Gibson-Corley; Curt D Sigmund; Justin L Grobe Journal: Am J Physiol Regul Integr Comp Physiol Date: 2018-01-24 Impact factor: 3.619