GABAergic excitation of vasopressin neurons

Possible mechanism underlying sodium-dependent hypertension

Young Beom Kim, 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

Research output: Contribution to journalArticle

35 Citations (Scopus)

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 languageEnglish
Pages (from-to)1296-1307
Number of pages12
JournalCirculation Research
Volume113
Issue number12
DOIs
Publication statusPublished - 2013 Dec 6

Fingerprint

Arginine Vasopressin
Vasopressins
Sodium
Hypertension
Neurons
Supraoptic Nucleus
Desoxycorticosterone
Salts
gamma-Aminobutyric Acid
Bumetanide
Acetates
GABA-A Receptors
GABA-A Receptor Agonists
Blood Pressure
Gramicidin
Muscimol
Pressoreceptors
Paraventricular Hypothalamic Nucleus
Microinjections
Chlorides

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 journalArticle

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. / GABAergic excitation of vasopressin neurons : Possible mechanism underlying sodium-dependent hypertension. In: Circulation Research. 2013 ; Vol. 113, No. 12. pp. 1296-1307.
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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

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KW - gamma-aminobutyric acid

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KW - NKCC1

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