ARTERIAL VERSUS VENOUS METABOLISM OF NITROGLYCERIN TO NITRIC-OXIDE - A POSSIBLE EXPLANATION OF ORGANIC NITRATE VENOSELECTIVITY

Nitroglycerin (NTG) and other organic nitrates are predominant venodil ators in vivo and in vitro. This selectivity is an important determina nt of their ability to relieve angina and congestive heart failure sym ptoms, but the mechanism of this phenomenon is unknown. Because organi c nitrate vasodilation occurs through metabolism to nitric oxide (NO), we tested the hypothesis that their venoselectivity is related to an enrichment of the pertinent enzyme in venous tissue; Enzymatic convers ion of NTG to NO was examined in microsomal fractions from bovine aort a as compared with vena cava tissues. NTG (150, 450, or 900 mu M) was incubated with 1 mg microsomal protein and glutathione (13 mu M), and cumulative NO production was measured for 5 h. When enzyme velocities were normalized to microsomal protein, statistical significance was no t observed between fractions from aorta and those from vena cava. Howe ver, when enzyme activity was normalized to tissue weight or total hom ogenate protein, statistically higher activity was observed in the ven ous tissue (p < 0.05). These differences were greatest (two- to three- fold higher in vena cava at all three NTG concentrations, p < 0.01) wh en enzyme velocity was normalized to the initial cellular content of t he homogenates (i.e., homogenate DNA concentrations). These results su ggest that organic nitrate venoselectivity may be at least partly expl ained by enrichment of the bioactivating enzyme in venous smooth muscl e cells.