Up-regulation of endothelial constitutive nitric oxide synthase expression by cyclic guanosine 31, 5' monophosphate

The role of cyclic GMP, the end product of the nitric oxide (NO)-cyclic GMP signalling pathway, in the molecular regulation of endothelial NO synthase (eNOS) expression was investigated. Bovine pulmonary endothelial cells were exposed to 8-bromo cyclic GMP and its effect on NO production, eNOS protein, and mRNA levels was analyzed. The eNOS activity was found to be significantly increased with the endothelial cells that were exposed to 8-bromo cyclic GMP. Also, endothelial cells on exposure to 8-bromo cyclic GMP produced significantly increased amounts of NO, detected as increased cyclic GMP in cocultures with vascular smooth muscle cells both under basal conditions and with agonist stimulation. 8-Bromo cyclic GMP significantly increased the eNOS protein and mRNA levels as detected on Western and Northern blots respectively. This 8-bromo cyclic GMP mediated increase of NO production, eNOS protein and mRNA levels suggests that cyclic GMP up-regulatcs the expression of eNOS. Thus, there may be an intercellular feedback mechanism involved at the molecular level in the expression of the NO-cyclic GMP signalling pathway in blood vessels.