PROTEIN-KINASE-C MODULATES MICROVASCULAR PERMEABILITY THROUGH NITRIC-OXIDE SYNTHASE

Protein kinase C (PKC) serves important functions in signal transducti on. We hypothesized that PKC modulation of microvascular permeability to macromolecules is mediated by nitric oxide (NO). To test this hypot hesis, we stimulated PKC topically with 10(-7) M phorbol 12,13-dibutyr ate (PDBu) in the hamster cheek pouch microcirculation. N-G-monomethyl -L-arginine (L-NMMA) at 10(-4) M was superfused in a bicarbonate buffe r solution throughout the experiment to inhibit the activity of NO syn thase. We evaluated changes in transport of fluorescein isothiocyanate -labeled 150,000 mol wt dextran by integrated optical intensity (IOI) using intravital fluorometry and computer-assisted digital image analy sis. Postcapillary areas were recorded. PDBu increased IOI from baseli ne to a value of 46.8 +/- 6.3 units (+/-SE). Pretreatment with L-NMMA decreased the PDBu-stimulated increment to 10.8 +/- 0.9 units. These r esults demonstrate that PKC-activated modulation of macromolecular tra nsport operates through a mechanism involving the production of NO.