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.

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