Regulation of the macromolecular transport in the brain microvessels: the role of cyclic GMP.

The possible effects of dibutyryl cyclic GMP (db-cGMP), the lipid-soluble derivative of cyclic GMP, on brain microvessels were studied by light microscopic detection of albumin and quantitative electron microscopy. Different concentrations (25, 50, 100 and 200 micrograms) of db-cGMP were given to adult rats by intracarotid infusion, while in the controls, the animals were infused either with Krebs-Ringer solution or with the same solution containing butyrate or cyclic GMP. In contrast to the controls, db-cGMP was found to be able to increase the permeability of brain microvessels to albumin in a dose-dependent manner. At the same time, the number of transport vesicles being indicative of the pinocytotic activity of the endothelial cells was also increased. These results indicate that, similarly to the cyclic AMP whose effects have been revealed earlier, the cyclic GMP-system may also be involved in the regulation of opening mechanisms of the blood-brain barrier.