Cyclic strain and forskolin differentially induce cAMP production in phenotypically diverse endothelial cells

The effects of cyclic strain and forskolin on cAMP production were studied in 4 endothelial cell types. Basal cAMP levels varied among the various types. Cyclic strain induced an increase in cAMP levels in endothelial cells isolated from bovine aortae, pig pulmonary arteries and human adipose microvessels, but not in endothelial cells isolated from human umbilical veins. 100 microM forskolin induced a differential increase in cAMP which ranged from 5-fold in pig pulmonary artery endothelial cells to 50-fold in human microvascular endothelial cells. Forskolin and cyclic strain, when applied to the cells concomitantly, had no additional effects on cAMP levels. However, when forskolin was applied 5 min after initiation of cyclic strain, a synergistic elevation of cAMP was observed in human umbilical vein endothelial cells. This action of forskolin was not mimicked by isoproterenol (10 microM). We suggest that the cAMP signalling system of phenotypically diverse endothelial cells is differentially regulated by cyclic strain and forskolin and that these differences might contribute to endothelial cell phenotypic diversity.