Protein kinase C inhibitors abolish the increased resistance of diabetic rat heart to ischemia-reperfusion injury.
Moon, CH; Jung, YS; Lee, SH; Baik, EJ
The Japanese journal of physiology, 49(5):409-415, 1999
The Japanese journal of physiology
Protein kinase C (PKC) has been implicated in ischemic preconditioning, but whether it plays a role in the cardioprotection observed in the diabetic heart is not known. We assessed the possible role of PKC by investigating whether the inhibition of PKC with staurosporine (Stau, 0.01 microM) or chelerythrine (Chel, 1 microM) can abolish the increased resistance to ischemia (25 min)-reperfusion (30 min) injury in Langendorff perfused hearts from streptozotocin-induced 4-week diabetic rats. In the diabetic heart, pre-ischemic left ventricular developed pressure (LVDP), double product (DP: LVDPxheart rate/1,000), +/- dP/dt(max) and coronary flow rate (CFR) were all reduced compared to the control. The pretreatment with Stau or Chel significantly improved these parameters. The post-ischemic contractile function was recovered to a greater extent in the diabetic heart (116.9 +/- 20.5% of pre-ischemic DP) than in the control (23.3 +/- 2.3% of pre-ischemic DP), indicating the increased resistance of the diabetic heart to ischemia-reperfusion injury. The treatment with Stau or Chel abolished the enhanced recovery in the diabetic heart (36.0 +/- 14.6 and 54.1 +/- 12.8% of pre-ischemic DP, respectively). The reduction in post-ischemic end diastolic pressure (EDP) and lactate dehydrogenase (LDH) release in diabetes (13.5 +/- 2.5 mmHg and 27.2 +/- 6.2 U/g heart) compared to the control (55.8 +/- 2.9 mmHg and 60. 3 +/- 5.7 U/g heart) was significantly (p<0.05) increased by pretreatment with Stau (39.0 +/- 4.9 mmHg and 53.1 +/- 7.6 U/g heart) or Chel (36.2 +/- 3.0 mmHg and 48.8 +/- 4.3 U/g heart). Neither Stau nor Chel had any influence on the post-ischemic values of LVDP, DP, +/- dP/dt(max), EDP and LDH release in the control heart. In the conclusion, the present results suggest that PKC activation may, at least in part, contribute to the increased resistance of the diabetic heart to ischemia-reperfusion injury.
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