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 (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. [(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 alpha(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.
Haywood
J R
JR
Department of Pharmacology, the University of Texas Health Science Center, San Antonio, Texas, USA. haywood@uthscsa.edu
Mifflin
S W
SW
Craig
T
T
Calderon
A
A
Hensler
J G
JG
Hinojosa-Laborde
C
C
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001665:Binding Sites; D001794:Blood Pressure / Q000187:drug effects; D002908:Chronic Disease; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D006339:Heart Rate / Q000187:drug effects; D006978:Hypertension, Renovascular / Q000097:blood / Q000378:metabolism*; D008297:Male; D008845:Microinjections; D009638:Norepinephrine / Q000097:blood; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D009638:Norepinephrine; D001640:Bicuculline