In vitro and ex vivo inhibitory effects of L- and D-enantiomers of NG-nitro-arginine on endothelium-dependent relaxation of rat aorta.

The in vitro and ex vivo inhibitory effects of NG-nitro-L-arginine (L-NNA) and NG-nitro-D-arginine (D-NNA) on endothelium-dependent relaxations were studied in rat aortic rings. L-NNA (3 x 10(-7) to 3 x 10(-5) M) but not D-NNA (3 x 10(-6) to 3 x 10(-4) M) induced contraction of resting aortic rings and potentiated phenylephrine-induced contraction in a concentration-dependent manner. In phenylephrine-preconstricted aortic rings, L-NNA (3 x 10(-7) to 3 x 10(-5) M) and D-NNA (3 x 10(-6) to 3 x 10(-4) M) concentration-dependently inhibited the relaxation response to acetylcholine (ACh) with similar efficacies and IC50 values of 10(-6) and 3.9 x 10(-5) M, respectively. In addition, both L-NNA (3 x 10(-5) M) and D-NNA (3 x 10(-4) M) almost totally inhibited the relaxation of preconstricted rings by the calcium ionophore A 23187. The inhibitory effects of L- and D-NNA remained for at least 4 hr after the preparations were washed out. Neither the inhibitory effects of L- and D-NNA on ACh-induced relaxation nor the ACh-induced relaxation itself were affected by pretreatment with indomethacin. However, pretreatment (10 min) or post-treatment (1 hr later) with L-Arg (10(-3) M) completely prevented or markedly reversed the inhibitory effects of L- and D-NNA.(ABSTRACT TRUNCATED AT 250 WORDS)