APStracts 2:0432H, 1995.

Protein kinase c inhibitors prevent endothelial dysfunction after myocardial ischemia/reperfusion in rats. Numaguchi, Kohtaro, Hiroaki Shimokawa, Ryuichi Nakaike, Kensuke Egashira, Akira Takeshita. Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University School of Medicine, Fukuoka, Japan

APStracts 2:0432H, 1995.

The intracellular mechanism 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, while endothelium-independent relaxations to SNP were unaffected. The 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.

Received 13 March 1995; accepted in final form 13 September 1995.
APS Manuscript Number H237-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 31 October 95