Production of endothelium-derived contracting factor is enhanced after coronary reperfusion.
To determine whether coronary reperfusion enhances the production of endothelium-derived contracting factor, we investigated dogs subjected to global cardiac ischemia (45 minutes) followed by reperfusion (60 minutes). Segments of reperfused and control coronary arteries were suspended in organ chambers to measure isometric force. Perfusate hypoxia caused endothelium-dependent contraction in the control and reperfused arteries. However, reperfused arteries exhibited hypoxic contraction that was significantly greater than control segments. The hypoxic contractions in both the control and reperfused arteries could be inhibited by NG-monomethyl-L-arginine (L-NMMA), the blocker of endothelial cell synthesis of nitric oxide from L-arginine. The action of L-NMMA could be reversed by L-arginine but not D-arginine. Thus, after reperfusion, augmented production of endothelium-derived contracting factor occurs by an L-arginine-dependent pathway. We hypothesize that nitric oxide produced by L-arginine metabolism combines with superoxide anion to produce the peroxynitrite anion (ONOO-), which is metabolized to endothelium-derived contracting factor or induces its synthesis. Augmented production of endothelium-derived contracting factor would favor vasospasm after reperfusion.
Pearson
P J
PJ
Section of Cardiovascular Surgery, Mayo Clinic, Rochester, MN 55905.
Lin
P J
PJ
Schaff
H V
HV
D000818:Animals; D001685:Biological Factors / Q000096:biosynthesis*; D002245:Carbon Dioxide / Q000494:pharmacology; D003329:Coronary Vasospasm / Q000209:etiology; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D016232:Endothelins / Q000096:biosynthesis*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular; D015425:Myocardial Reperfusion; D009584:Nitrogen / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology
D001685:Biological Factors; D016232:Endothelins; D002245:Carbon Dioxide; D015237:Dinoprost; D009584:Nitrogen; D010100:Oxygen