Microvascular permeability and number of tight junctions are modulated by cAMP

We tested the hypothesis that increased endothelial cell adenosine 3′,5′-cyclic monophosphate (cAMP) decreases microvascular permeability in vivo. The effects of cAMP-specific phosphodiesterase type IV inhibition and adenylate cyclase activation on microvascular hydraulic conductivity ( L p) were investigated in intact individual capillaries and postcapillary venules in mesentery of pithed frogs ( Rana pipiens ). Treatment with rolipram (10 μM) and forskolin (5 μM) for 25 min decreased L p to 37% of control. Rolipram alone also significantly decreased L p. Isoproterenol (10 μM) decreased L p to 27% of control within 20 min. A subgroup of eight vessels treated with rolipram and forskolin, in which mean L p fell to 25% of control, was examined with transmission electron microscopy. The mean number of tight junctions in the treated vessels was 2.2 per cleft (303 clefts), significantly higher than in a matched control group (192 clefts), which was 1.7 per cleft. The results indicate that microvascular L pcan be modulated by intracellular cAMP and that one of the structural end points of stimulated cAMP levels is an increase in the mean number of tight-junction strands between endothelial cells.