Effects of Second Messengers on the Permeability and Morphology of Eel Rete Capillaries

The effects of second-messenger concentration changes on capillary diffusion capacity (permeability-surface area product [PS]) to cellular and paracellular tracers and on capillary ultrastructure were studied during countercurrent perfusion of the rete of the eel swim bladder. Cyclic nucleotide effects were investigated with isoproterenol, forskolin, and dibutyryl cAMP. Isoproterenol (5 times 10 6 mol/L) did not modify water and solute permeability or capillary structure. Forskolin (10 4 mol/L) immediately raised the concentrations of cAMP in the rete and produced interstitial edema but did not change permeability. The addition of dibutyryl cAMP (10 6 mol/L) to the perfusate had rapid effectsit reduced the PS of [sup 3 H]water and oxygen and increased the PS of [sup 125 I]albumin, [sup 14 C]sucrose, and Na. No structural changes were observed. Phosphoinositide effects were studied with 1,2-dioctanoyl-sn-glycerol (DG) and phorbol 12-myristate 13-acetate (PMA). DG (10 5 mol/L) had no effect on the permeability of the rete to water and solutes, while inducing cell membrane vacuolization. PMA (10 5 mol/L) progressively reduced the PS of [sup 3 H]water. In contrast, PS values of [sup 125 I]albumin, [sup 14 C]sucrose, and Na rose gradually. Membrane vacuoles bulging into the lumen and in the cytoplasm were a common feature. The Ca plus effect was investigated with the Ca plus ionophore A23187. At 5 times 10 6 mol/L, unsteady permeability changes and extensive cytolysis were observed. At 5 times 10 7 mol/L, the PS of [sup 125 I]albumin, [sup 14 C]sucrose, and Na rapidly increased. The PS values for water were not modified. No structural changes were identified. It is concluded that increments of second-messenger concentrations in the rete induce characteristic selective effects on the paracellular and transcellular pathways of transport and create significant but nonselective alterations of capillary structure.(Circ Res. 1995;76:566-574.)