Prostacyclin and Thromboxane in Non-Insulin Dependent Diabetes: The Chlorpropamide Alcohol Flush Reaction Revisited

1. Levels of immunoreactive 6-oxo-prostaglandin F_1α (6-oxo-PGF_1α) and thromboxane B₂ (TXB₂) were measured in peripheral venous plasma in a group of volunteers and non-insulin dependent diabetic patients (NIDDS). Levels of these eicosanoids were close to the limit of sensitivity of the radioimmunoassays and consequently data are reported as maximal values. Basal plasma levels of 6-oxo-PGF_1α did not exceed 5 pg/ml in either group and maximal levels of immunoreactive TXB₂ were 125 ± 14 and 128 ± 8 pg/ml for volunteers and NIDDS respectively.

2. Attempts to elicit peripheral vascular prostacyclin biosynthesis in volunteers by using forearm ischaemia produced no increase in plasma 6-oxo-PGF_1α levels. Measurement of the combined plasma levels of 6-oxo-PGF_1α, 13,14-dihydro-6-oxo-PGF_1α, 13,14-dihydro-6,15-dioxo-PGF_1α and 6-oxo-PGE₁ indicated that these were also low (less than 5 pg/ml) and that failure to demonstrate increased 6-oxo-PGF_1α levels was unlikely to have arisen from metabolism of prostacyclin to one or more of these metabolites.

3. Measurement of 6-oxo-PGF_1α and TXB₂ in peripheral venous plasma before and during chloropropamide alcohol flushing (CPAF) did not provide evidence for a role for these eicosanoids in the etiology of this phenomenon.

4. These findings point to the need for a reappraisal of studies that have described altered plasma levels of 6-oxo-PGF_1α and TXB₂ in CPAF and other pathophysiological conditions in man.