Effects of cyclic GMP on microvascular permeability of the cerebral cortex

This study was performed to test the hypothesis that a direct application of cyclic guanosine monophosphate (cGMP) to the cortex would increase blood-brain barrier (BBB) permeability. Rats were anesthetized with 1.4% isoflurane and were mechanically ventilated. Two cranial windows (3 mm in diameter) were made on each side of the rat's skull (a total of four windows on each rat) to expose the cerebral cortex. A patch of normal saline, 10(-5) M, 10(-4) M, or 10(-3) M 8-bromo-cGMP was applied to each cranial window. The patches were changed every 5 min. Ten minutes after applying the patches, BBB permeability was determined by measuring the transfer coefficient (Ki) of [alpha-14C]aminoisobutyric acid. Vital signs were not changed after applying 8-bromo-cGMP. Blood gases were within normal limits. In the cortex, 10(-5) M 8-bromo-cGMP did not significantly affect the Ki; 10(-4) M 8-bromo-cGMP increased the Ki by 115%; 10(-3) M 8-bromo-cGMP increased the Ki by 124%. However, there was no statistical difference in the Ki between the doses of 10(-4) M and 10(-3) M 8-bromo-cGMP. In the pons where no patch was applied, the Ki was similar to that of the cortical area where a normal saline patch was applied. Our data demonstrated that a direct application of cGMP to the cerebral cortex significantly increased the permeability of the BBB.