Iseproterenol mimics calcium preconditioning-induced protection against ischemia

Hiroshi Miyawaki, Muhammad Ashraf

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Abstract

We tested the hypothesis that a transient increase in intracellular calcium concentration ([Ca2+](i)) before prolonged ischemia triggers the activation of protein kinase C (PKC), resulting in significant protection against ischemic injury. Ca2+ preconditioning (3 cycles of 1-min Ca2+ depletion and 5-min Ca2+ repletion) and pharmacological intervention with isoproterenol (Iso) were employed to increase the Ca2+ influx. Langendorff- perfused rat hearts were subjected to 40 min of global ischemia followed by 30 min of reperfusion (I/R). A significant functional recovery and minimal biochemical changes were observed in Ca2+-preconditioned hearts after I/R. Pretreatment with 0.1 μmol/l Iso caused a sudden increase in left ventricular contractility, a significant decrease in lactate dehydrogenase release, preservation of ATP content, and left ventricular function compared with nontreated I/R hearts. Administration of verapamil during Iso treatment blunted the salutary effects of Iso on I/R and pretreatment with BAY K 8644, an L-type Ca2+-channel opener, mimicked Iso-induced protection. Addition of propranolol or specific PKC inhibitors (chelerythrine or bisindolylmaleimide) during Iso infusion completely abolished the beneficial effects of Iso. These results demonstrate that 1) treatment with a low dose of Iso provides significant protection against ischemic injury, 2) transient elevation of [Ca2+](i) is a strong activator of PKC, and 3) PKC plays a crucial role in the subcellular mechanisms of protection by activating second messenger signals during Iso-induced preconditioning.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume272
Issue number2 41-2
StatePublished - Feb 1 1997
Externally publishedYes

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Keywords

  • BAY K 8644
  • protein kinase C

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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