氨基酸可使灌注的大鼠肠系膜的阻力血管扩张。

Amino acids dilate resistance blood vessels of the perfused rat mesentery.

作者信息

al-Swayeh O A, Moore P K

机构信息

Biomedical Sciences Division, King's College, University of London, UK.

出版信息

J Pharm Pharmacol. 1989 Oct;41(10):723-6. doi: 10.1111/j.2042-7158.1989.tb06351.x.

DOI:10.1111/j.2042-7158.1989.tb06351.x

PMID:2575155

Abstract

The vasodilator effect of several L-amino acids in the perfused, noradrenaline-preconstricted rat mesentery preparation has been investigated. N-alpha-Benzoyl-L-arginine ethyl ester (BAEE) (ED50, 1.4 +/- 0.09 mumol) and L-alanine methylester (ED50, 0.9 +/- 0.007 mumol) were the most potent although L-arginine methylester, hydroxamate and hydrochloride, N-alpha-benzoyl-L-arginine methyl ester (BAME), L-methionine methylester, L-lysine hydroxamate and L-glutamic acid methylester exhibited similar potency with ED50 values in the range 2.4-3.7 mumol. L-Homoarginine chloride was inactive at doses up to 20 mumols. D-Arginine hydrochloride and D-lysine hydroxamate were inactive at doses up to 50 mumols whilst D-methionine methylester (50 mumols) produced small falls in perfusion pressure in only 3 out of 7 preparations studied. Responses to BAEE, BAME, L-arginine hydrochloride, L-alanine methylester, L-methionine methylester, L-lysine hydroxamate and acetylcholine (but not nitroprusside) were significantly inhibited by CHAPS (4.7 mg mL-1, 30 s) de-endothelialization as well as pretreatment of mesentery preparations with gossypol (3 microM). Responses to BAEE, BAME, L-arginine hydrochloride, L-alanine methylester and acetylcholine were similarly selectively reduced by NDGA (10 microM) pretreatment. We propose that these L-amino acids exhibit vasodilator activity in the perfused rat mesentery by virtue of releasing endothelium-derived nitric oxide (EDNO).

摘要

研究了几种L-氨基酸在灌注的、去甲肾上腺素预收缩的大鼠肠系膜制备物中的血管舒张作用。N-α-苯甲酰-L-精氨酸乙酯（BAEE）（半数有效剂量[ED50]，1.4±0.09 μmol）和L-丙氨酸甲酯（ED50，0.9±0.007 μmol）是最有效的，尽管L-精氨酸甲酯、异羟肟酸盐和盐酸盐、N-α-苯甲酰-L-精氨酸甲酯（BAME）、L-蛋氨酸甲酯、L-赖氨酸异羟肟酸盐和L-谷氨酸甲酯表现出相似的效力，ED50值在2.4 - 3.7 μmol范围内。L-高精氨酸盐酸盐在高达20 μmol的剂量下无活性。D-精氨酸盐酸盐和D-赖氨酸异羟肟酸盐在高达50 μmol的剂量下无活性，而D-蛋氨酸甲酯（50 μmol）仅在7个研究的制备物中的3个中引起灌注压力的小幅下降。用CHAPS（4.7 mg/mL，30秒）去内皮以及用棉酚（3 μM）预处理肠系膜制备物后，对BAEE、BAME、L-精氨酸盐酸盐、L-丙氨酸甲酯、L-蛋氨酸甲酯、L-赖氨酸异羟肟酸盐和乙酰胆碱（但不是硝普钠）的反应受到显著抑制。用NDGA（10 μM）预处理后，对BAEE、BAME、L-精氨酸盐酸盐、L-丙氨酸甲酯和乙酰胆碱的反应同样被选择性降低。我们提出，这些L-氨基酸通过释放内皮衍生的一氧化氮（EDNO）在灌注的大鼠肠系膜中表现出血管舒张活性。