Fasudil prevents KATP channel-induced improvement in postischemic functional recovery

Kenya Nishizawa, Paul E. Wolkowicz, Tadashi Yamagishi, Ling Ling Guo, Martin Pike

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Whereas activation of ATP-dependent potassium (KATP) channels greatly improves postischemic myocardial recovery, the final effector mechanism for KATP channel-induced cardioprotection remains elusive. RhoA is a GTPase that regulates a variety of cellular processes known to be involved with KATP channel cardioprotection. Our goal was to determine whether the activity of a key rhoA effector, rho kinase (ROCK), is required for K ATP channel-induced cardioprotection. Four groups of perfused rat hearts were subjected to 36 min of zero-flow ischemia and 44 min of reperfusion with continuous measurements of mechanical function and 31P NMR high-energy phosphate data: 1) untreated, 2) pinacidil (10 μM) to activate KATP channels, 3) fasudil (15 μM) to inhibit ROCK, and 4) both fasudil and pinacidil. Pinacidil significantly improved postischemic mechanical recovery [39 ± 16 vs. 108 ± 4 mmHg left ventricular diastolic pressure (LVDP), untreated and pinacidil, respectively]. Fasudil did not affect reperfusion LVDP (41 ± 13 mmHg) but completely blocked the marked improvement in mechanical recovery that occurred with pinacidil treatment (54 ± 15 mmHg). Substantial attenuation of the postischemic energetic recovery was also observed. These data support the hypothesis that ROCK activity plays a role in KATP channel-induced cardioprotection.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume288
Issue number6 57-6
DOIs
StatePublished - Jun 2005
Externally publishedYes

Fingerprint

Pinacidil
KATP Channels
Ventricular Pressure
Reperfusion
Adenosine Triphosphate
Blood Pressure
rho-Associated Kinases
GTP Phosphohydrolases
Potassium Channels
Ischemia
Phosphates
fasudil

Keywords

  • Cardioprotection
  • Fasudil
  • Pinacidil
  • Rho kinase

ASJC Scopus subject areas

  • Physiology

Cite this

Fasudil prevents KATP channel-induced improvement in postischemic functional recovery. / Nishizawa, Kenya; Wolkowicz, Paul E.; Yamagishi, Tadashi; Guo, Ling Ling; Pike, Martin.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 288, No. 6 57-6, 06.2005.

Research output: Contribution to journalArticle

Nishizawa, Kenya ; Wolkowicz, Paul E. ; Yamagishi, Tadashi ; Guo, Ling Ling ; Pike, Martin. / Fasudil prevents KATP channel-induced improvement in postischemic functional recovery. In: American Journal of Physiology - Heart and Circulatory Physiology. 2005 ; Vol. 288, No. 6 57-6.
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