ACTIVATION OF THE ADENYLYL CYCLASE CYCLIC AMP/PROTEIN KINASE-A PATHWAY IN ENDOTHELIAL-CELLS EXPOSED TO CYCLIC STRAIN/

The aim of this study was to assess the involvement of the adenylyl cy clase/cyclic AMP/protein kinase A pathway (AC) in endothelial cells (E C) exposed to different levels of mechanical strain. Bovine aortic EC were seeded to confluence on flexible membrane-bottom wells. The membr anes were deformed with either 150 mm Hg (average 10% strain) or 37.5 mm Hg (average 6% strain) vacuum at 60 cycles per minute (0.5 s strain ; 0.5 s relaxation) for 0-60 min. The results demonstrate that at 10% average strain (but not 6% average strain) there was a 1.5- to 2.2-fol d increase in AC, cAMP, and PKA activity by 15 min when compared to un stretched controls. Further studies revealed an increase in cAMP respo nse element binding protein in EC subjected to the 10% average strain (but not 6% average strain). These data support the hypothesis that cy clic strain activates the AC/cAMP/PKA signal transduction pathway in E C which may occur by exceeding a strain threshold and suggest that cyc lic strain may stimulate the expression of genes containing cAMP-respo nsive promoter elements. (C) 1997 Academic Press.