(Hypertension. 2001;37:614.)
© 2001 American Heart Association, Inc.
Scientific Contributions |
-Aminobutyric Acid (GABA)-A Function and Binding in the Paraventricular Nucleus of the Hypothalamus in Chronic Renal-Wrap Hypertension
From the Department of Pharmacology, the University of Texas Health Science Center, San Antonio.
Correspondence to Joseph R. Haywood, PhD, Department of Pharmacology, the University of Texas Health Science Center, 7703 Floyd Curl Dr, San Antonio, TX 78229-3900. E-mail haywood{at}uthscsa.edu
The
goal of this study was to determine whether 
-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<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 
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.
Key Words: [3H]flunitrazepam • sympathetic nervous system • bicuculline • receptors
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