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

Citation
Wg. Mayhan et Sp. Didion, ACTIVATION OF PROTEIN-KINASE-C DOES NOT PARTICIPATE IN DISRUPTION OF THE BLOOD-BRAIN-BARRIER TO ALBUMIN DURING ACUTE HYPERTENSION, Brain research, 696(1-2), 1995, pp. 106-112
Citations number
38
Categorie Soggetti
Neurosciences
Journal title
ISSN journal
00068993
Volume
696
Issue
1-2
Year of publication
1995
Pages
106 - 112
Database
ISI
SICI code
0006-8993(1995)696:1-2<106:AOPDNP>2.0.ZU;2-7
Abstract
The blood-brain barrier minimizes the entry of macromolecules into bra in tissue. During acute increases in arterial blood pressure, disrupti on of the blood-brain barrier occurs primarily in cerebral venules and veins. Mechanisms by which increases in cerebral venous pressure prod uce disruption of the blood-brain barrier during acute hypertension ar e not clear. The goal of this study was to determine the role of activ ation of protein kinase C in disruption of the blood-brain barrier dur ing acute hypertension. We examined the microcirculation of the cerebr um in vivo. Permeability of the blood-brain barrier was quantitated by the formation of venular leaky sites and clearance of fluorescent-lab eled albumin (FITC-albumin) before and during phenylephrine-induced ac ute hypertension. In addition, we examined changes in pial arteriolar and pial venular pressure before and during phenylephrine-induced acut e hypertension. We compared responses of the blood-brain barrier to ac ute 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 visi ble and clearance of FITC-albumin was minimal in all groups. Phenyleph rine infusion increased systemic arterial, pial arteriolar and pial ve nular pressures, and increased the formation of venular leaky sites an d clearance of FITC-albumin by a similar magnitude in all groups. The findings of the present study suggest that inhibition of protein kinas e C does not significantly alter the formation of venular leaky sites and/or clearance of FITC-albumin during acute hypertension. Thus, disr uption of the blood-brain barrier during acute hypertension does not a ppear to be influenced by activation of protein kinase C.