Vasospasm following subarachnoid hemorrhage: evidence against functional upregulation of protein kinase C constrictor pathway.
This study tested the hypothesis that vasospasm due to subarachnoid hemorrhage involves the functional upregulation of protein kinase C. Spasm of the rabbit basilar artery was achieved using a double hemorrhage model, which we previously demonstrated was endothelin-1 dependent. In situ effects of agents were determined by direct measurement of vessel diameter following their suffusion in a cranial window. Chelerythrine, a protein kinase C inhibitor, relaxed the spasm. However, relaxations to chelerythrine were not significantly greater in endothelin-1 constricted spastic vessels initially relaxed with the endothelin converting enzyme inhibitor, phosphoramidon, as compared to endothelin-1 constricted control vessels. These results suggest that subarachnoid hemorrhage induced vasospasm does not involve functional upregulation of protein kinase C.
Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, PO Box 670575, Cincinnati, OH 45267-0575, USA.
SeongHun
S
Yoon
Mario
M
Zuccarello
Robert M
RM
Rapoport
D000470:Alkaloids; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000378:metabolism; D053119:Benzophenanthridines; D019332:Endothelin-1 / Q000378:metabolism / Q000494:pharmacology; D004791:Enzyme Inhibitors; D006020:Glycopeptides / Q000494:pharmacology; D008297:Male; D010617:Phenanthridines / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D011817:Rabbits; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000201:enzymology; D015854:Up-Regulation; D014661:Vasoconstriction / Q000187:drug effects*; D020301:Vasospasm, Intracranial / Q000201:enzymology* / Q000209:etiology*
D000470:Alkaloids; D053119:Benzophenanthridines; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D006020:Glycopeptides; D010617:Phenanthridines; D011480:Protease Inhibitors; C016299:chelerythrine; D011493:Protein Kinase C; C008890:phosphoramidon