Evidence of an endogenous forebrain GABAergic system capable of inhibiting baroreceptor-mediated vasopressin release.
In conscious rats, intracerebroventricular (i.c.v.) injections of gamma-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 micrograms) caused dose-related reductions in MAP (5 +/- 1.7 +/- 1 and 11 +/- 2 mm Hg, respectively). Nipecotic acid (3-350 micrograms) 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 micrograms). Hypotension induced by CEI + CHLOR caused a significant increase in pAVP. Forebrain-restricted nipecotic acid significantly suppressed pAVP (61 +/- 8% reduction; P less than 0.05 vs aCSF). These data provide evidence of an endogenous forebrain GABAergic system which, when activated, can inhibit baroreceptor-mediated AVP release.
Segura
T
T
University of Texas Health Science Center, Department of Pharmacology, San Antonio 78284.
Hasser
E M
EM
Shade
R E
RE
Haywood
J R
JR
D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism*; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009557:Nipecotic Acids / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects / Q000502:physiology*; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000502:physiology*
D009557:Nipecotic Acids; D001127:Arginine Vasopressin; C030278:nipecotic acid; D005680:gamma-Aminobutyric Acid; D011392:Proline; C010983:homoproline