UP-REGULATION OF ENDOTHELIAL NITRIC-OXIDE SYNTHASE EXPRESSION BY CYCLIC GUANOSINE 3',5'-MONOPHOSPHATE

In this study, the role of cyclic GMP, the end product of the NO-cycli c GMP signalling pathway, in the regulation of ecNOS was investigated, Bovine pulmonary endothelial cells were exposed to 8-bromo-cyclic GMP and its effect on NO production, ecNOS protein, and mRNA levels was a nalyzed, Endothelial cells on exposure to 8-bromo-cyclic GMP produced significantly increased amounts of NO, detected as increased cyclic GM P in cocultures with vascular smooth muscle cells both under basal con ditions and with agonist stimulation. 8-Bromo-cyclic GMP significantly increased the ecNOS protein and mRNA levels as detected on Western an d Northern blots respectively, This 8-bromo-cyclic GMP mediated increa se of NO production, ecNOS protein and mRNA levels suggests that cycli c GMP up-regulates the expression of ecNOS, Thus, there may be an inte rcellular feedback mechanism involved at the molecular level in the ex pression of the NO-cyclic GMP signalling pathway in blood vessels.