Vasospasm following subarachnoid hemorrhage: evidence against functional upregulation of Rho kinase constrictor pathway.
This study tested the hypothesis that vasospasm due to subarachnoid hemorrhage involves the functional upregulation of Rho kinase. 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. Y-27632, a Rho kinase inhibitor, relaxed the spasm. However, relaxations to Y-27632 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, at least in the rabbit double subarachnoid hemorrhage model, vasospasm does not involve the functional upregulation of Rho kinase.
Yoon
Seonghun
S
Department of Pharmacology and Cell Biophyscis, University of Cincinnati College of Medicine, OH 45267-0575, USA.
Sherman
Jonathan D
JD
Zuccarello
Mario
M
Rapoport
Robert M
RM
D000577:Amides / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects; D019332:Endothelin-1 / Q000494:pharmacology; D006020:Glycopeptides / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009125:Muscle Relaxants, Central / Q000493:pharmacokinetics / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011725:Pyridines / Q000493:pharmacokinetics / Q000494:pharmacology*; D011817:Rabbits; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*; D020301:Vasospasm, Intracranial / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D054460:rho-Associated Kinases
D000577:Amides; D019332:Endothelin-1; D006020:Glycopeptides; D047908:Intracellular Signaling Peptides and Proteins; D009125:Muscle Relaxants, Central; D011480:Protease Inhibitors; D011725:Pyridines; C108830:Y 27632; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; C008890:phosphoramidon