Contractile activity and prostacyclin generation in isolated coronary arteries from diabetic dogs

The present study was aimed at determining the generation of "prostacyclin (PGI2)-like-material" in coronary arteries from normal and diabetic (pancreatectomized) dogs as well as the contractile responses to prostacyclin of preparations from normal, diabetic and insulin-treated diabetic animals. PGI2 produced a dose-dependent relaxation of coronary arteries from normal dogs. In contrast, those from diabetic animals were not related; indeed, at low concentrations PGI2 failed to evoke any effect but at higher ones it induced a distinct contraction. In arteries from diabetic animals treated with insulin, PGI2 induced a biphasic contractile effect, which lay between that of normal controls and untreated diabetics. In addition the basal generation of "PGI2-like-material" by coronary arteries was significantly higher in the diabetic (141 +/- 0.2 pg/mg, mean +/- SEM) than in normal dogs (59 +/- 0.2 pg/mg). The present experiments demonstrate that the generation of "PGI2-like substance" is significantly increased in coronary arteries from diabetic dogs, but the same vessels are unable to respond to added authentic PGI2 with relaxation; on the contrary they react with a distinct positive contractile response.