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

29 Citations (Scopus)

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
Pages (from-to)H1634-H1639
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume270
Issue number5 39-5
DOIs
Publication statusPublished - 1996

All Science Journal Classification (ASJC) codes

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

Fingerprint Dive into the research topics of 'PKC inhibitors prevent endothelial dysfunction after myocardial ischemia-reperfusion in rats'. Together they form a unique fingerprint.

  • Cite this