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 GABAA 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 (GABAA 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.
| Original language | English |
|---|---|
| Pages (from-to) | 1296-1307 |
| Number of pages | 12 |
| Journal | Circulation Research |
| Volume | 113 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 2013 Dec 6 |
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Keywords
- arginine vasopressin
- gamma-aminobutyric acid
- hypertension
- NKCC1
- sodium
- supraoptic nucleus
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
Cite this
GABAergic excitation of vasopressin neurons : Possible mechanism underlying sodium-dependent hypertension. / Kim, Young Beom; Kim, Yoon Sik; Kim, Woong Bin; Shen, Feng Yan; Lee, Seung Won; Chung, Hyun Joo; Kim, Jeong Sook; Han, Hee Chul; Colwell, Christopher S.; Kim, Yang In.
In: Circulation Research, Vol. 113, No. 12, 06.12.2013, p. 1296-1307.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - GABAergic excitation of vasopressin neurons
T2 - Possible mechanism underlying sodium-dependent hypertension
AU - Kim, Young Beom
AU - Kim, Yoon Sik
AU - Kim, Woong Bin
AU - Shen, Feng Yan
AU - Lee, Seung Won
AU - Chung, Hyun Joo
AU - Kim, Jeong Sook
AU - Han, Hee Chul
AU - Colwell, Christopher S.
AU - Kim, Yang In
PY - 2013/12/6
Y1 - 2013/12/6
N2 - 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 GABAA 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 (GABAA 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.
AB - 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 GABAA 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 (GABAA 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.
KW - arginine vasopressin
KW - gamma-aminobutyric acid
KW - hypertension
KW - NKCC1
KW - sodium
KW - supraoptic nucleus
UR - http://www.scopus.com/inward/record.url?scp=84890435055&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84890435055&partnerID=8YFLogxK
U2 - 10.1161/CIRCRESAHA.113.301814
DO - 10.1161/CIRCRESAHA.113.301814
M3 - Article
VL - 113
SP - 1296
EP - 1307
JO - Circulation Research
JF - Circulation Research
SN - 0009-7330
IS - 12
ER -