Protein kinase C ßII peptide inhibitor exerts cardioprotective effects in rat cardiac ischemia/reperfusion injury
Ischemia followed by reperfusion (I/R) in the presence of polymorphonuclear leukocytes (PMNs) results in a marked cardiac contractile dysfunction. A cell-permeable protein kinase C (PKC) ßII peptide inhibitor was used to test the hypothesis that PKC ßII inhibition could attenuate PMN-induced cardiac dysfunction by suppression of superoxide production from PMNs and increase NO release from vascular endothelium. The effects of the PKC ßII peptide inhibitor were examined in isolated ischemic (20 min) and reperfused (45 min) rat hearts with PMNs. The PKC ßII inhibitor (10 µM; n = 7) significantly attenuated PMN-induced cardiac dysfunction compared with I/R hearts (n = 9) receiving PMNs alone in left ventricular developed pressure (LVDP) and the maximal rate of LVDP (+dP/dtmax) cardiac function indices (p < 0.01). The PKC ßII inhibitor at 10 µM significantly increased endothelial NO release from a basal value of 1.85 ± 0.18 pmol NO/mg tissue to 3.49 ± 0.62 pmol NO/mg tissue from rat aorta. It also significantly inhibited superoxide release (i.e., absorbance) from N-formyl-L-methionyl-L-leucyl-L-phenylalanine-stimulated rat PMNs from 0.13 ± 0.01 to 0.02 ± 0.004 (p < 0.01) at 10 µM. Histological analysis of the left ventricle of representative rat hearts from each group showed that the PKC ßII peptide inhibitor-treated hearts experienced a marked reduction in PMN vascular adherence and infiltration into the postreperfused cardiac tissue compared with I/R + PMN hearts (p < 0.01). These results suggest that the PKC ßII peptide inhibitor attenuates PMN-induced post-I/R cardiac contractile dysfunction by increasing endothelial NO release and by inhibiting superoxide release from PMNs.
Journal of Pharmacology and Experimental Therapeutics
Omiyi, Didi; Brue, Richard J.; Taormina, Philip II; Harvey, Margaret; Atkinson, Norrell; and Young, Lindon, "Protein kinase C ßII peptide inhibitor exerts cardioprotective effects in rat cardiac ischemia/reperfusion injury" (2005). PCOM Scholarly Papers. 460.