Protein kinase C inhibition attenuates vascular ETB receptor upregulation and decreases brain damage after cerebral ischemia in rat.
BACKGROUND
Protein kinase C (PKC) is known to be involved in the pathophysiology of experimental cerebral ischemia. We have previously shown that after transient middle cerebral artery occlusion, there is an upregulation of endothelin receptors in the ipsilateral middle cerebral artery. The present study aimed to examine the effect of the PKC inhibitor Ro-32-0432 on endothelin receptor upregulation, infarct volume and neurology outcome after middle cerebral artery occlusion in rat.


RESULTS
At 24 hours after transient middle cerebral artery occlusion (MCAO), the contractile endothelin B receptor mediated response and the endothelin B receptor protein expression were upregulated in the ipsilateral but not the contralateral middle cerebral artery. In Ro-32-0432 treated rats, the upregulated endothelin receptor response was attenuated. Furthermore, Ro-32-0432 treatment decreased the ischemic brain damage significantly and improved neurological scores. Immunohistochemistry showed fainter staining of endothelin B receptor protein in the smooth muscle cells of the ipsilateral middle cerebral artery of Ro-32-0432 treated rats compared to control.


CONCLUSIONS
The results suggest that treatment with Ro-32-0432 in ischemic stroke decreases the ischemic infarction area, neurological symptoms and associated endothelin B receptor upregulation. This provides a new perspective on possible mechanisms of actions of PKC inhibition in cerebral ischemia.
Henriksson
Marie
M
Division of Experimental Vascular Research, Department of Clinical Sciences in Lund, Lund University, Sweden. Marie.Henriksson@med.lu.se
Stenman
Emelie
E
Vikman
Petter
P
Edvinsson
Lars
L
D000818:Animals; D001284:Atrophy / Q000378:metabolism / Q000517:prevention & control; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology*; D002560:Cerebrovascular Circulation; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044023:Receptor, Endothelin B / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D007211:Indoles; D011758:Pyrroles; D044023:Receptor, Endothelin B; C085989:Ro 32-0432; D011493:Protein Kinase C