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
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.