Activation of protein kinase C does not participate in disruption of the blood-brain barrier to albumin during acute hypertension.

Abstract

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.

• Authors: W G Mayhan, S P Didion
• Journal: Brain research (Brain Res) Vol. 696 Issue 1-2 Pg. 106-12 (Oct 23 1995) ISSN: 0006-8993 [Print] Netherlands
• PMID: 8574657 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Enzyme Inhibitors
• Naphthalenes
• Phorbol 12,13-Dibutyrate
• Protein Kinase C
• calphostin C
• Sphingosine

Topics

• Acute Disease
• Animals
• Blood Pressure (drug effects)
• Blood-Brain Barrier (physiology)
• Capillary Permeability (physiology)
• Enzyme Activation (physiology)
• Enzyme Inhibitors (pharmacology)
• Hypertension (physiopathology)
• Male
• Naphthalenes (pharmacology)
• Phorbol 12,13-Dibutyrate (pharmacology)
• Protein Kinase C (antagonists & inhibitors, metabolism)
• Rats
• Rats, Sprague-Dawley
• Sphingosine (pharmacology)