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

The goal of this study was to determine whether gamma -aminobutyric acid (G ABA)ergic transmission and GABA binding are altered in chronic renal-wrap h ypertension. Three groups of hypertensive and sham-operated rats were prepa red for separate protocols. Four weeks later, the animals were prepared wit h femoral artery catheters for the measurement of mean arterial pressure. I n all groups, blood pressure was significantly higher in the renal-wrapped animals. In the first study, bilateral microinjection of the GABA-A antagon ist, bicuculline (50 pmol/site), into the parsventricular nucleus of the hy pothalamus (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 b pm, P=0.064) in hypertensive rats. [H-3]Flunitrazepam was used to measure b inding to the GABA-A receptor, Magnocellular neurons and the adjacent media l parvicellular neurons had more intense binding compared with the remainde r 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 t hese parameters between normotensive and hypertensive animals. Competitive reverse transcription-polymerase chain reaction was used to measure the exp ression of mRNA for the <alpha>(1) subunit of the GABA-A receptor. No diffe rence 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 expressi on of the number or affinity to the receptor. These findings suggest that t he greater GABAergic activity is the result of an increase in GABA release in the PVN in chronic renal-wrap hypertension.