Amino acids dilate resistance blood vessels of the perfused rat mesentery

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).