Evidence of an endogenous forebrain GABAergic system capable of inhibiting baroreceptor-mediated vasopressin release

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.