APStracts 3:0305H, 1996.

Protein kinase c modulates microvascular permeability through nitric oxide synthase . Ram_rez, Mar_a M., David D. Kim, and Walter N. Dur_n. Program in Vascular Biology; Departments of Pharmacology and Physiology, of Medicine, and of Surgery; UMDNJ - New Jersey Medical School; Newark, New Jersey 07103-2714

APStracts 3:0305H, 1996.

Protein kinase C (PKC) serves important functions in signal transduction. We hypothesized that PKC modula tion of microvascular permeability to macromolecules is mediated by NO. To test this hypothesis, we stimulat ed PKC topically with 10-7M phorbol dibutyrate (PDBu) in the hamster cheek pouch microcirculation. L -nitro-monomethyl arginine (L-NMMA) at 10-4M was superfused in a bicarbonate buffer solution throughout the experiment to inhibit the activity of NO synthase. We evaluated changes in transport of FITC -Dextran 150 by integrated optical intensity (IOI) using intravital fluorometry and computer-assisted digital image analysis. Postcapillary areas were recorded. PDBu increased IOI from baseline to a value of 46.8 +/- 6.3 units (mean +/- SEM). Pretreatment with L -NMMA decreased the PDBu-stimulated increment to 10.8 +/- 0.9 units. These results demonstrate that PKC-activated modulation of macromolecular transport operates through a mechanism involving the production of NO.

Received 16 May 1996; accepted in final form 24 June 1996.
APS Manuscript Number H448-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996