Abstract
In conscious rats, intracerebroventricular (i.c.v.) injections of γ-aminobutyric acid (GABA), a GABA-uptake inhibitor (nipecotic acid), and artificial CSF (aCSF) were restricted to forebrain regions and their effect on baroreceptor-mediated arginine-vasopressin (AVP) release was studied. AVP release was stimulated by the hypotension resulting from combined treatment with a converting enzyme inhibitor (CEI) and chlorisondamine (CHLOR), a ganglionic blocking agent. CEI + CHLOR reduced mean arterial pressure (MAP) from 118±2 to 63±2 mm Hg, but pressure then rose to a compensated level of 78±1 mm Hg. The compensation in MAP was shown to be AVP-dependent at the end of the experiment since the vascular AVP antagonist, d(CH2)5Tyr(Me)AVP, reduced MAP from 78±1 to 63±1 mm Hg. While AVP was contributing to MAP maintenance, GABA (15, 50 and 150 μg) caused dose-related reductions in MAP (5±1,7±1 and 11±2 mm Hg, respectively). Nipecotic acid (3-350 μg) also caused dose-related reductions in MAP (from 3±1 to 15±2 mm Hg), while aCSF had no effect on MAP. Pretreatment with d(CH2)5Tyr(Me)AVP, antagonized completely the depressor effects of GABA and nipecotic acid. In other rats, blood samples were taken to measure the changes in plasma AVP concentrations (pAVP) induced by CEI + CHLOR and subsequent treatment with aCSF or nipecotic acid (175 μg). Hypotension induced by CEI + CHLOR caused a significant increase in pAVP. Forebrain-restricted nipecotic acid significantly suppressed pAVP (61 ± 8% reduction; P < 0.05 vs aCSF). These data provide evidence of an endogenous forebrain GABAergic system which, when activated, can inhibit baroreceptor-mediated AVP release.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 53-62 |
| Number of pages | 10 |
| Journal | Brain Research |
| Volume | 499 |
| Issue number | 1 |
| DOIs | |
| State | Published - Oct 9 1989 |
| Externally published | Yes |
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Keywords
- Arginine-vasopressin
- Baroreceptor
- Cardiovascular regulation
- Chlorisondamine
- Converting enzyme inhibition
- γ-Aminobutyric acid
ASJC Scopus subject areas
- Developmental Biology
- Molecular Biology
- Clinical Neurology
- Neuroscience(all)
Cite this
Evidence of an endogenous forebrain GABAergic system capable of inhibiting baroreceptor-mediated vasopressin release. / Segura, Ted; Hasser, Eileen M.; Shade, Robert E.; Haywood, Joseph R.
In: Brain Research, Vol. 499, No. 1, 09.10.1989, p. 53-62.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Evidence of an endogenous forebrain GABAergic system capable of inhibiting baroreceptor-mediated vasopressin release
AU - Segura, Ted
AU - Hasser, Eileen M.
AU - Shade, Robert E.
AU - Haywood, Joseph R.
PY - 1989/10/9
Y1 - 1989/10/9
N2 - In conscious rats, intracerebroventricular (i.c.v.) injections of γ-aminobutyric acid (GABA), a GABA-uptake inhibitor (nipecotic acid), and artificial CSF (aCSF) were restricted to forebrain regions and their effect on baroreceptor-mediated arginine-vasopressin (AVP) release was studied. AVP release was stimulated by the hypotension resulting from combined treatment with a converting enzyme inhibitor (CEI) and chlorisondamine (CHLOR), a ganglionic blocking agent. CEI + CHLOR reduced mean arterial pressure (MAP) from 118±2 to 63±2 mm Hg, but pressure then rose to a compensated level of 78±1 mm Hg. The compensation in MAP was shown to be AVP-dependent at the end of the experiment since the vascular AVP antagonist, d(CH2)5Tyr(Me)AVP, reduced MAP from 78±1 to 63±1 mm Hg. While AVP was contributing to MAP maintenance, GABA (15, 50 and 150 μg) caused dose-related reductions in MAP (5±1,7±1 and 11±2 mm Hg, respectively). Nipecotic acid (3-350 μg) also caused dose-related reductions in MAP (from 3±1 to 15±2 mm Hg), while aCSF had no effect on MAP. Pretreatment with d(CH2)5Tyr(Me)AVP, antagonized completely the depressor effects of GABA and nipecotic acid. In other rats, blood samples were taken to measure the changes in plasma AVP concentrations (pAVP) induced by CEI + CHLOR and subsequent treatment with aCSF or nipecotic acid (175 μg). Hypotension induced by CEI + CHLOR caused a significant increase in pAVP. Forebrain-restricted nipecotic acid significantly suppressed pAVP (61 ± 8% reduction; P < 0.05 vs aCSF). These data provide evidence of an endogenous forebrain GABAergic system which, when activated, can inhibit baroreceptor-mediated AVP release.
AB - In conscious rats, intracerebroventricular (i.c.v.) injections of γ-aminobutyric acid (GABA), a GABA-uptake inhibitor (nipecotic acid), and artificial CSF (aCSF) were restricted to forebrain regions and their effect on baroreceptor-mediated arginine-vasopressin (AVP) release was studied. AVP release was stimulated by the hypotension resulting from combined treatment with a converting enzyme inhibitor (CEI) and chlorisondamine (CHLOR), a ganglionic blocking agent. CEI + CHLOR reduced mean arterial pressure (MAP) from 118±2 to 63±2 mm Hg, but pressure then rose to a compensated level of 78±1 mm Hg. The compensation in MAP was shown to be AVP-dependent at the end of the experiment since the vascular AVP antagonist, d(CH2)5Tyr(Me)AVP, reduced MAP from 78±1 to 63±1 mm Hg. While AVP was contributing to MAP maintenance, GABA (15, 50 and 150 μg) caused dose-related reductions in MAP (5±1,7±1 and 11±2 mm Hg, respectively). Nipecotic acid (3-350 μg) also caused dose-related reductions in MAP (from 3±1 to 15±2 mm Hg), while aCSF had no effect on MAP. Pretreatment with d(CH2)5Tyr(Me)AVP, antagonized completely the depressor effects of GABA and nipecotic acid. In other rats, blood samples were taken to measure the changes in plasma AVP concentrations (pAVP) induced by CEI + CHLOR and subsequent treatment with aCSF or nipecotic acid (175 μg). Hypotension induced by CEI + CHLOR caused a significant increase in pAVP. Forebrain-restricted nipecotic acid significantly suppressed pAVP (61 ± 8% reduction; P < 0.05 vs aCSF). These data provide evidence of an endogenous forebrain GABAergic system which, when activated, can inhibit baroreceptor-mediated AVP release.
KW - Arginine-vasopressin
KW - Baroreceptor
KW - Cardiovascular regulation
KW - Chlorisondamine
KW - Converting enzyme inhibition
KW - γ-Aminobutyric acid
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UR - http://www.scopus.com/inward/citedby.url?scp=0024424941&partnerID=8YFLogxK
U2 - 10.1016/0006-8993(89)91134-7
DO - 10.1016/0006-8993(89)91134-7
M3 - Article
C2 - 2804669
AN - SCOPUS:0024424941
VL - 499
SP - 53
EP - 62
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 1
ER -