REGULATION OF BLOOD-BRAIN-BARRIER ENDOTHELIAL-CELLS BY NITRIC-OXIDE

Nitric oxide (NO) synthesized by vascular endothelial cells is a poten t vasodilator substance. The actions of NO extend well beyond its vaso dilatory properties, and increasingly, NO has been recognized as an im portant signal for intercellular and intracellular communication. Rece ntly, NO has been implicated in the regulation of vascular and blood-b rain barrier permeability. NO has also been shown to modulate ion chan nels in excitable cells, thus affecting neuronal firing. We report the results of patch-clamp experiments that show a modulatory action of N O as well as cGMP and cAMP on a hyperpolarization-activated current (I -ha) carried by both Na+ and K+ ions in blood-brain barrier endothelia l cells. I-ha was recorded in cells dialyzed with 0.2 mmol/L GTP-gamma -S to inhibit a large inwardly rectifying potassium current. This ioni c current and its modulation by NO may play a role in the regulation o f the transport of ions, nutrients, and other molecules to the brain a nd serve as an integral part of the blood-brain barrier. The modulatio n of I-ha by a cyclic guanosine nucleotide may also explain previous r eports suggesting a role for NO in the regulation of blood-brain barri er function.