Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Vincelette, J. et al.

Inhibition of rho-kinase by hydroxyfasudil prevents vasopressin-induced myocardial ischemia in Donryu rats by attenuating coronary vasoconstriction.

BACKGROUND: Inhibition of rho-kinase has been shown to attenuate vasopressin (AVP)-induced myocardial ischemia measured as S-wave depression in Donryu rats. This has been attributed to a direct inhibitory effect on AVP-induced coronary vasoconstriction. However, since AVP also increased mean arterial blood pressure (MAP) which was attenuated by the rho-kinase inhibitors used, the prevention of myocardial ischemia could have been due to effects on afterload. RESULTS: The purpose of this study was to determine if rho-kinase inhibition prevents S-wave depression independent of the effects on blood pressure. In anesthetized Donryu rats (200-340 g), infusion of AVP (0.1 IU/kg) resulted in a sustained increase in MAP (DeltaMAP=46+/-7 mm Hg) and a transient S-wave depression (-90+/-20 microV). Infusion of phenylephrine titrated to achieve a comparable pressor response (DeltaMAP=52+/-2 mm Hg) resulted in a significantly smaller S-wave depression (-30+/-20 microV). Pretreatment with the rho-kinase inhibitor, hydroxyfasudil (3 mg/kg), decreased MAP by -28+/-2 mm Hg and significantly attenuated AVP-induced S-wave depression (-10+/-10 microV) compared to AVP. When rats were pretreated with phenylephrine titrated to maintain MAP, hydroxyfasudil still significantly attenuated AVP-induced S-wave depression (-14+/-12 microV). Hydralazine (1 mg/kg), which lowered MAP by -36+/-5 mm Hg, had no significant effect on AVP-induced S-wave depression (-105+/-32 microV). CONCLUSION:These data indicate that inhibition of rho-kinase with hydroxyfasudil attenuates AVP-induced myocardial ischemia independent of changes in MAP and are consistent with an inhibitory effect on coronary vasoconstriction.[1]

References

Inhibition of rho-kinase by hydroxyfasudil prevents vasopressin-induced myocardial ischemia in Donryu rats by attenuating coronary vasoconstriction. Vincelette, J., Pagila, R., Kawai, K., Ishii, M., Horimizu, Y., Vergona, R., Sullivan, M.E., Morser, J., Dole, W.P., Wang, Y.X. Pharmacology (2005) [Pubmed]

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