γ-Aminobutyric acid (GABA)-A function and binding in the paraventricular nucleus of the hypothalamus in chronic renal-wrap hypertension

Joseph R. Haywood, Steven W. Mifflin, Teresa Craig, Alfred Calderon, Julie G. Hensler, Carmen Hinojosa-Laborde

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

The goal of this study was to determine whether γ-aminobutyric acid (GABA)ergic transmission and GABA binding are altered in chronic renal-wrap hypertension. Three groups of hypertensive and sham-operated rats were prepared for separate protocols. Four weeks later, the animals were prepared with femoral artery catheters for the measurement of mean arterial pressure. In all groups, blood pressure was significantly higher in the renal-wrapped animals. In the first study, bilateral microinjection of the GABA-A antagonist, bicuculline (50 pmol/site), into the paraventricular nucleus of the hypothalalnus (PVN) caused a greater increase in arterial pressure (21.9±1.4 versus 16.7± 1.8 mm Hg, P<0.05) and heart rate (135±15 versus 98±12 bpm, P=0.064) in hypertensive rats. [3H] Flunitrazepam was used to measure binding to the GABA-A receptor. Magnocellular neurons and the adjacent medial parvicellular neurons had more intense binding compared with the remainder of the PVN. Bmax was greater for the higher density binding area; the Kd value was less in the high-density region. There were no differences in these parameters between normotensive and hypertensive animals. Competitive reverse transcription-polymerase chain reaction was used to measure the expression of mRNA for the α1 subunit of the GABA-A receptor. No difference was observed in the mRNA between renal-wrapped and sham-operated rats. In summary, inhibition of GABA-A receptors in the PVN is augmented in the chronic phase of hypertension and is unrelated to a change in the expression of the number or affinity to the receptor. These findings suggest that the greater GABAergic activity is the result of an increase in GABA release in the PVN in chronic renal-wrap hypertension.

Original languageEnglish (US)
Pages (from-to)614-618
Number of pages5
JournalHypertension
Volume37
Issue number2 II
DOIs
StatePublished - 2001

Keywords

  • Bicuculline
  • Receptors
  • Sympathetic nervous system
  • [H]flunitrazepam

ASJC Scopus subject areas

  • Internal Medicine

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