PKC inhibitors prevent endothelial dysfunction after myocardial ischemia-reperfusion in rats

Kohtaro Numaguchi, Hiroaki Shimokawa, Ryuichi Nakaike, Kensuke Egashira, Akira Takeshita

Research output: Contribution to journalArticle

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Abstract

The intracellular mecha-nism for endothelial dysfunction after myocardial ischemia-reperfusion remains to be elucidated. It has been reported that activation of protein kinase C (PKC) occurs after myocardial ischemia-reperfusion and that the activation impairs endothelium-dependent relaxation. Thus we examined the role of PKC activation in the ischemia-reperfusion-induced endothelial dysfunction. Isolated rat hearts perfused with a constant flow were subjected to global ischemia for 15 min followed by reperfusion for 20 min. Coronary vascular responses to the endothelium-dependent vasodilators acetylcholine (ACh) and bradykinin (BK) and the endothelium-independent vasodilator sodium nitroprusside (SNP) were examined before and after the ischemia-reperfusion. Endothelium-dependent relaxations to ACh and BK were impaired after the ischemia-reperfusion, whereas endothelium-independent relaxations to SNP were unaffected. Pretreatment with a PKC inhibitor, staurosporine, H7, or calphostin C, prevented the impairments. Phorbol 12-myristate 13-acetate, a PKC-activating phorbol ester, attenuated the relaxations to ACh and BK but not those to SNP. These results suggest that PKC activation may be involved in part in the ischemia-reperfusion-induced endothelial dysfunction.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume270
Issue number5 39-5
Publication statusPublished - 1996

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Myocardial Reperfusion
Protein C Inhibitor
Protein Kinase Inhibitors
Protein Kinase C
Reperfusion
Myocardial Ischemia
Ischemia
Endothelium
Nitroprusside
Bradykinin
Acetylcholine
Endothelium-Dependent Relaxing Factors
Staurosporine
Phorbol Esters
Vasodilator Agents
Blood Vessels
Acetates

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

Cite this

PKC inhibitors prevent endothelial dysfunction after myocardial ischemia-reperfusion in rats. / Numaguchi, Kohtaro; Shimokawa, Hiroaki; Nakaike, Ryuichi; Egashira, Kensuke; Takeshita, Akira.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 270, No. 5 39-5, 1996.

Research output: Contribution to journalArticle

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