Yamada K, Moriguchi A, Mikami H, Okuda N, Higaki J, Ogihara T
Department of Geriatric Medicine, Osaka University Medical School, Japan.
J Hypertens. 1995 Dec;13(12 Pt 2):1624-30.
To investigate the effects of central amino acid neurons on the antihypertensive action of a newly developed angiotensin II type 1 receptor (AT1) antagonist, CV 11974.
We measured the release of various amino acids in the rostral ventrolateral medulla using the brain microdialysis technique. A microdialysis probe was inserted into the exposed rostral ventrolateral medulla in male spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats anaesthetized with urethane. Mean arterial pressure and the release of amino acids (glutamate, glycine, glutamine, taurine and gamma-aminobutyric acid) were monitored before and after intravenous administration of CV 11974 (5 mg/kg), nitroglycerin (5 mu g/kg per min) or vehicle.
In SHR, CV 11974 decreased mean arterial pressure (-40 +/- 6 mmHg) accompanied by significant increases in the release of inhibitory amino acids, glycine (411 +/- 83%) and gamma-aminobutyric acid (363 +/- 71%) in the rostral ventrolateral medulla, whereas intravenous nitroglycerin produced a decrease in mean arterial pressure (-35 +/- 4 mmHg) without changes in amino acid release. In WKY rats, both intravenous CV 11974 and intravenous nitroglycerin produced smaller but significant decreases in mean arterial pressure (CV 11974, -18 +/- 5 mmHg; nitroglycerin, -20 +/- 7 mmHg) without change in the release of amino acids in the rostral ventrolateral medulla. Selective perfusion of glycine or gamma-aminobutyric acid into the rostral ventrolateral medulla caused a larger mean arterial pressure reduction in SHR than in WKY rats. Furthermore, the use of a specific antagonist of glycine or of the gamma-aminobutyric acid receptor in the rostral ventrolateral medulla attenuated the antihypertensive response induced by the intravenous AT1 antagonist in SHR.
The present results suggest that the release of the inhibitory amino acids glycine and gamma-aminobutyric acid in the rostral ventrolateral medulla contributes to the depressor action of this AT1 receptor antagonist in the genetic hypertensive rat model.
研究中枢氨基酸能神经元对新开发的1型血管紧张素II受体（AT1）拮抗剂CV 11974降压作用的影响。
我们采用脑微透析技术测量延髓头端腹外侧区多种氨基酸的释放。将微透析探针插入用乌拉坦麻醉的雄性自发性高血压大鼠（SHR）和Wistar - Kyoto（WKY）大鼠暴露的延髓头端腹外侧区。在静脉注射CV 11974（5mg/kg）、硝酸甘油（5μg/kg每分钟）或溶剂前和后监测平均动脉压以及氨基酸（谷氨酸、甘氨酸、谷氨酰胺、牛磺酸和γ-氨基丁酸）的释放。
在SHR中，CV 11974使平均动脉压降低（-40±6mmHg），同时延髓头端腹外侧区抑制性氨基酸甘氨酸（411±83%）和γ-氨基丁酸（363±71%）的释放显著增加，而静脉注射硝酸甘油使平均动脉压降低（-35±4mmHg），氨基酸释放无变化。在WKY大鼠中，静脉注射CV 11974和静脉注射硝酸甘油均使平均动脉压有较小但显著的降低（CV 11974，-18±5mmHg；硝酸甘油，-20±7mmHg），延髓头端腹外侧区氨基酸释放无变化。向延髓头端腹外侧区选择性灌注甘氨酸或γ-氨基丁酸导致SHR的平均动脉压降低幅度大于WKY大鼠。此外，在延髓头端腹外侧区使用甘氨酸或γ-氨基丁酸受体的特异性拮抗剂可减弱静脉注射AT1拮抗剂在SHR中诱导的降压反应。
目前的结果表明，延髓头端腹外侧区抑制性氨基酸甘氨酸和γ-氨基丁酸的释放有助于该AT1受体拮抗剂在遗传性高血压大鼠模型中的降压作用。
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