Enhanced responses to endothelin during perfusion of ischemic myocardium. Myocardial response to endothelin.
Although endothelin perfusion at 50 pM did not reduce the coronary flow, at 200 pM, it reduced the coronary flow to a similar extent in both normal and ischemic hearts. Endothelin at 50 pM concentration enhanced the myocardial levels of inositol-1,4,5-triphosphate (IP3) and diacyl glycerol (DG) in ischemic, but not in normal, hearts. On the other hand, endothelin at 50 pM concentration enhanced the activities of membrane protein kinase C (PKC) and calmodulin dependent (CaM-PK) kinases in normal, but not in ischemic, hearts. The corresponding loss of cytosolic PKC, but not of CaM-PK, suggests a translocation of PKC and an activation of CaM-PK by endothelin. These results suggest that pM concentrations of endothelin activate membrane kinases in normal hearts and enhance PIP2, breakdown in ischemic hearts. The greater CK release and myocardial levels of nonesterified fatty acids by 200 pM concentrations of endothelin in ischemic hearts, as compared to control hearts, suggests that: (1) the myocardial cellular injury and phospholipid breakdown induced by pM concentrations of endothelin are enhanced during reperfusion; and (2) both IP3 and membrane kinase (PKC and CaM-PK) dependent biochemical cascades of reaction, rather than kinases alone, may be involved in the endothelin-induced myocardial cellular injury.
Jones
R M
RM
Department of Surgery, University of Connecticut Health Center, Farmington 06030-9984.
Prasad
M R
MR
D000704:Analysis of Variance; D000818:Animals; D003326:Coronary Circulation / Q000502:physiology; D003402:Creatine Kinase / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D016232:Endothelins / Q000502:physiology*; D004789:Enzyme Activation / Q000502:physiology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D004075:Diglycerides; D016232:Endothelins; D005230:Fatty Acids, Nonesterified; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D015544:Inositol 1,4,5-Trisphosphate; D011494:Protein Kinases; D003402:Creatine Kinase