ACTIVATION OF PROTEIN-KINASE-C DOES NOT PARTICIPATE IN DISRUPTION OF THE BLOOD-BRAIN-BARRIER TO ALBUMIN DURING ACUTE HYPERTENSION

The blood-brain barrier minimizes the entry of macromolecules into brain tissue. During acute increases in arterial blood pressure, disruption of the blood-brain barrier occurs primarily in cerebral venules and veins. Mechanisms by which increases in cerebral venous pressure produce disruption of the blood-brain barrier during acute hypertension are not clear. The goal of this study was to determine the role of activation of protein kinase C in disruption of the blood-brain barrier during acute hypertension. We examined the microcirculation of the cerebrum in vivo. Permeability of the blood-brain barrier was quantitated by the formation of venular leaky sites and clearance of fluorescent-labeled albumin (FITC-albumin) before and during phenylephrine-induced acute hypertension. In addition, we examined changes in pial arteriolar and pial venular pressure before and during phenylephrine-induced acute hypertension. We compared responses of the blood-brain barrier to acute hypertension in control (untreated) rats and in rats treated with inhibitors of protein kinse C; calphostin C (0.1 mu M) or sphingosine (1.0 mu M). Under control conditions, no venular leaky sites were visible and clearance of FITC-albumin was minimal in all groups. Phenylephrine infusion increased systemic arterial, pial arteriolar and pial venular pressures, and increased the formation of venular leaky sites and clearance of FITC-albumin by a similar magnitude in all groups. The findings of the present study suggest that inhibition of protein kinase C does not significantly alter the formation of venular leaky sites and/or clearance of FITC-albumin during acute hypertension. Thus, disruption of the blood-brain barrier during acute hypertension does not appear to be influenced by activation of protein kinase C.