Segura T, Hasser E M, Shade R E, Haywood J R
University of Texas Health Science Center, Department of Pharmacology, San Antonio 78284.
Brain Res. 1989 Oct 9;499(1):53-62. doi: 10.1016/0006-8993(89)91134-7.
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.
在清醒大鼠中，将γ-氨基丁酸（GABA）、一种GABA摄取抑制剂（尼克酸）和人工脑脊液（aCSF）脑室内（i.c.v.）注射局限于前脑区域，并研究它们对压力感受器介导的精氨酸加压素（AVP）释放的影响。联合使用转化酶抑制剂（CEI）和神经节阻断剂氯异吲哚铵（CHLOR）进行治疗所导致的低血压刺激了AVP的释放。CEI + CHLOR使平均动脉压（MAP）从118±2降至63±2 mmHg，但随后血压升至78±1 mmHg的代偿水平。在实验结束时，MAP的代偿显示依赖于AVP，因为血管AVP拮抗剂d(CH2)5Tyr(Me)AVP使MAP从78±1降至63±1 mmHg。当AVP有助于维持MAP时，GABA（15、50和150微克）导致MAP出现剂量相关的降低（分别为5±1、7±1和11±2 mmHg）。尼克酸（3 - 350微克）也导致MAP出现剂量相关的降低（从3±1降至15±2 mmHg），而aCSF对MAP没有影响。用d(CH2)5Tyr(Me)AVP进行预处理完全拮抗了GABA和尼克酸的降压作用。在其他大鼠中，采集血样以测量由CEI + CHLOR以及随后用aCSF或尼克酸（175微克）治疗所诱导的血浆AVP浓度（pAVP）的变化。CEI + CHLOR诱导的低血压导致pAVP显著增加。局限于前脑的尼克酸显著抑制了pAVP（降低61±8%；与aCSF相比，P<0.05）。这些数据提供了内源性前脑GABA能系统的证据，该系统被激活时可抑制压力感受器介导的AVP释放。
