Vasospasm following subarachnoid hemorrhage: evidence against functional upregulation of Rho kinase constrictor pathway

Neurol Res. 2002 Jun;24(4):392-4. doi: 10.1179/016164102101200078.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amides / pharmacokinetics
  • Amides / pharmacology*
  • Animals
  • Basilar Artery / drug effects
  • Endothelin-1 / pharmacology
  • Glycopeptides / pharmacology
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Muscle Relaxants, Central / pharmacokinetics
  • Muscle Relaxants, Central / pharmacology*
  • Protease Inhibitors / pharmacology
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / metabolism*
  • Pyridines / pharmacokinetics
  • Pyridines / pharmacology*
  • Rabbits
  • Subarachnoid Hemorrhage / complications
  • Subarachnoid Hemorrhage / metabolism
  • Vasoconstriction / drug effects*
  • Vasospasm, Intracranial / enzymology*
  • Vasospasm, Intracranial / etiology
  • Vasospasm, Intracranial / pathology
  • rho-Associated Kinases

Substances

  • Amides
  • Endothelin-1
  • Glycopeptides
  • Intracellular Signaling Peptides and Proteins
  • Muscle Relaxants, Central
  • Protease Inhibitors
  • Pyridines
  • Y 27632
  • Protein Serine-Threonine Kinases
  • rho-Associated Kinases
  • phosphoramidon