Isoproterenol mimics calcium preconditioning-induced protection against ischemia

Hiroshi Miyawaki, Muhammad Ashraf

Research output: Contribution to journalArticle

Abstract

We tested the hypothesis that a transient increase in intracellular calcium concentration ((Ca 2+ ] i ) before prolonged ischemia triggers the activation of protein kinase C (PKC), resulting in significant protection against ischemic injury. Ca 2+ preconditioning (3 cycles of 1-min Ca 2+ depletion and 5-min Ca 2+ repletion) and pharmacological intervention with isoproterenol (Iso) were employed to increase the Ca 2+ 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 Ca 2+ -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 Ca 2+ -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 ischémie injury, 2) transient elevation of [Ca 2+ ] 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
Volume272
Issue number2 PART 2
StatePublished - Dec 1 1997
Externally publishedYes

Fingerprint

Isoproterenol
Ischemia
Calcium
Protein Kinase C
Protein C Inhibitor
Wounds and Injuries
Second Messenger Systems
Protein Kinase Inhibitors
Verapamil
Left Ventricular Function
L-Lactate Dehydrogenase
Propranolol
Reperfusion
Adenosine Triphosphate
Pharmacology

Keywords

  • BAY K 8644
  • Protein kinase c

ASJC Scopus subject areas

  • Physiology (medical)

Cite this

Isoproterenol mimics calcium preconditioning-induced protection against ischemia. / Miyawaki, Hiroshi; Ashraf, Muhammad.

In: American Journal of Physiology, Vol. 272, No. 2 PART 2, 01.12.1997.

Research output: Contribution to journalArticle

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