γ-Aminobutyric Acid (GABA)-A Function and Binding in the Paraventricular Nucleus of the Hypothalamus in Chronic Renal-Wrap Hypertension

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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 hypothalamus (PVN) caused a greater increase in arterial pressure (21.9±1.4 versus 16.7±1.8 mm Hg, P P =0.064) in hypertensive rats. [ 3 H]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. B max was greater for the higher density binding area; the K d 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 α 1 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.