Simulating the diabetic environment modifies in vitro prostacyclin synthesis

To explain the contradictory data on the secretion of prostacyclin (PGI₂) in clinical and experimental diabetes, we have investigated the effect of each of the major metabolic abnormalities in uncontrolled diabetes on vascular PGI₂ synthesis. An increase in fatty acid concentrations caused a dose-dependent inhibition of PGI₂ synthesis by rat aortic rings in vitro; linoleic and linolenic acids were consistently the most and palmitic the least inhibitory. Glucose had a stimulatory effect between 10 and 30 mmol/L, but a progressive fall in stimulation occurred at higher concentrations. Insulin was inhibitory at 10 and 50 mU/L; however, in combination with glucose (10 mmol/L) it was significantly stimulatory (at 10 mU/L) when the aortic rings were preincubated for 2 and 4 h. A pH of 7.0 or less was significantly inhibitory, whereas ketone bodies had no significant effect on PGI₂ synthesis. These data show for the first time that altered metabolic factors in uncontrolled diabetes may have different effects on vascular PGI₂ synthesis. These data help explain the variability of observations related to PGI₂ synthesis and secretion in diabetes, and advocate a more detailed definition of the metabolic status of patients/animals used in such experiments.