Evidence that contractions of isolated arteries by L-NMMA and NOLA are not due to inhibition of basal EDRF release

Abstract

We have tested the hypothesis that endothelium-dependent contractions to two L-arginine analogues modified in either of the guanidino nitrogens [e.g., N(G)-monomethyl-L-arginine (L-NMMA) and N(ω)-nitro-L-arginine (NOLA)] are due to inhibition of basally released EDRF. We found that these contractions in the dog isolated coronary artery were maximal at 10 μM for each compound, as increasing the concentration 10-fold further gave no significant increase in developed force. Over the same concentration range, NOLA was more potent than L-NMMA in blocking relaxations to the endothelium-dependent agonist, acetylcholine. Thus, for L-NMMA, only the highest concentrations (30-100 μM) caused a small bu..