Protein kinase C modulates microvascular permeability through nitric oxide synthase.
Protein kinase C (PKC) serves important functions in signal transduction. We hypothesized that PKC modulation of microvascular permeability to macromolecules is mediated by nitric oxide (NO). To test this hypothesis, we stimulated PKC topically with 10(-7) M phorbol 12,13-dibutyrate (PDBu) in the hamster check pouch microcirculation. NG-monomethyl-L-arginine (L-NMMA) at 10(-4) M was superfused in a bicarbonate buffer solution throughout the experiment to inhibit the activity of NO synthase. 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 analysis. Postcapillary areas were recorded. PDBu increased IOI from baseline 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 results demonstrate that PKC-activated modulation of macromolecular transport operates through a mechanism involving the production of NO.
Department of Pharmacology and Physiology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark 07103-2714, USA.
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Ramírez
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Kim
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Durán
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D002610:Cheek / Q000098:blood supply; D006224:Cricetinae; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000502:physiology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D015240:Phorbol 12,13-Dibutyrate; D019001:Nitric Oxide Synthase; D011493:Protein Kinase C