Development of antihypertensive drugs: L-arginine and its derivatives as a precursor of endothelium-derived relaxing factor

抗高血压药物的开发：L-精氨酸及其衍生物作为内皮源性舒张因子的前体

• 批准号: 03557012
• 负责人: NAKAKI Toshio
• 金额: $ 7.49万
• 依托单位: KEIO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research (B)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03557012/
• 关键词: L-arginine; Antihypertensive drug; Nitric oxide; EDRF; Plasma cGMP; Nitrite; nitrate; Citrulline; Endothelium; 原発性アルドステロン症; 腎血管性高血圧症; 一酸化窒素(NO)

Intravenous administration of L-arginine to normotensive healthy volunteers caused a slight reduction of systemic blood pressure. To essential and secondary hypertension it caused a marked decrease in systemic blood pressure. Based on observations of the increase in plasma cyclic GMP and citrulline, as well as urinary nitrite/nitrate and increased output of nitric oxide from cultured endothelial cells, the antihypertensive effect of L-arginine was probably due to an increase in nitric oxide synthesis/release in vivo. L-arginine suppressed plasma aldosterone. These results suggest that exogenous L-arginine produces a vasodilatory effect by increasing NO production and that L-arginine or released NO modulates the release of neuroendocrine hormones in hypertensive subjects.

正常血压的健康志愿者静脉注射L-精氨酸可使全身血压轻微降低。对原发性和继发性高血压，它引起全身血压显着下降。根据对血浆环GMP和瓜氨酸增加以及尿亚硝酸盐/硝酸盐和培养内皮细胞一氧化氮输出增加的观察，L-精氨酸的降压作用可能是由于体内一氧化氮合成/释放增加。L-精氨酸抑制血浆醛固酮。这些结果表明，外源性L-精氨酸产生血管舒张作用，通过增加NO的产生和L-精氨酸或释放NO调节高血压受试者的神经内分泌激素的释放。

项目成果

K. Hishikawa, T. Nakaki, H. Suzuki, T. Saruta and R. Kato: "Effect of systemic L-arginine administration on hemodynamics and nitric oxide release in man" Jpn. Heart J.33. 41-48 (1992)

K. Hishikawa、T. Nakaki、H. Suzuki、T. Saruta 和 R. Kato：“全身性 L-精氨酸给药对人体血流动力学和一氧化氮释放的影响”Jpn。

Hishikawa,K.: "Effect of systemic L-arginine administration on hemodynamic and nitric oxide release in man" Jpn.Heart J.(1992)

Hishikawa,K.：“全身 L-精氨酸给药对人体血流动力学和一氧化氮释放的影响”Jpn.Heart J.(1992)

SUZUKI,H.: "Increases in NO_2-NO_3- excreation in the urine as an indicator of the release of endothelium-derived relaxing factor during elevation of blood pressure" Clin.Sci.82. 631-634 (1992)

SUZUKI,H.：“尿液中 NO_2-NO_3- 排泄的增加作为血压升高期间内皮衍生舒张因子释放的指标”Clin.Sci.82。

H. Suzuki, H. Ikenaga, K. Hishikawa, T. Nakaki, R. Kato and T. Saruta: "Increases in NO2^-/NO3^- excretion in the urine as an indicator of the release of endothelium-derived relaxing factor during elevation of blood pressure." Clin Sci. 82. 631-634 (1992)

H. Suzuki、H. Ikenaga、K. Hishikawa、T. Nakaki、R. Kato 和 T. Saruta：“尿液中 NO2^-/NO3^- 排泄量的增加是内皮源性松弛因子释放的指标

K. Hishikawa, T. Nakaki, H. Suzuki, T. Saruta and R. Kato: "L-arginine-induced hypotension" Lancet. 337. 683-684 (1991)

K. Hishikawa、T. Nakaki、H. Suzuki、T. Saruta 和 R. Kato：“L-精氨酸引起的低血压”《柳叶刀》。