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 kinase C; calphostin C (0.1 microM) or sphingosine (1.0 microM). 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.
Mayhan
W G
WG
Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha 68198-4575, USA.
Didion
S P
SP
D000208:Acute Disease; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000502:physiology*; D002199:Capillary Permeability / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013110:Sphingosine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D009281:Naphthalenes; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; C058819:calphostin C; D013110:Sphingosine