THE EFFECTS OF L-ARGININE AND NG-NITRO-L-ARGININE METHYL-ESTER (L-NAME) ON NITROGLYCEROL TOLERANCE AFTER SHORT AND LONG INCUBATION OF ISOLATED BOVINE ABDOMINAL-AORTA

In preparations of isolated bovine abdominal aorta incubated for only 30 min. L-arginine (10(-4) mol. 1-1) by itself produced no effect or only occasionally a slight relaxation, both in control and nitroglycerol (NTG) - tolerant preparations. Neither L-arginine nor L-NAME (N(g)-nitro-L-arginine methyl ester) 10(-4) mol. 1-1) affected significantly the mechanical responsiveness of the aorta to NTG in NTG-toelrant preparations incubated for a short period of time. Contrary to this, in preparations previously exposed to a long period of ncubation (4-5 hours, 37-degrees-C, aeration with 95% O2 + 5% CO2), L-arginine by itself produced relaxation of the aorta. The relaxing effect of L-arginine was more pronounced in NTG-tolerant preparations than in the non-tolerant controls. In NTG-tolerant preparations, after 4-5 hours of incubation, L-arginine significantly reversed the state of tolerance, thus making the toelrant aorta more responsive to NTG than in te tolerant preparations. The experiments indicate that after a short period of incubation, nitric oxide does not seem to play a role in the acute NTG tolerance. After a prolonged period of incubation of the isolated aorta, L-arginine-nitric oxide (NO)-pathways seem to operate, indicating their possible role in the acute NTG tolerance. The relaxations evoked by L-arginine were impaired by L-NAME, an inhibitor of conversion of L-arginine to NO, and by methylene blue, an inhibitor of soluble guanylate cyclase. These results indicate that the relaxing effect of L-arginine in long-term-incubated bovine abdominal aorta is specific and implicates an activation of the L-arginine-NO-pathways. Both endothelial and smooth muscle cells possess L-arginine-NO-pathways, but those in the muscle cells are more easily affected by L-NAME and by methylene blue than those in the endothelial cells.