The influence of oral hypoglycaemic sulfonyl ureas on prostacyclin release by the rat thoracic aorta.
The influence of some oral hypoglycaemic sulfonyl ureas on PGI2 release by the rat thoracic aorta in vitro was examined using reversed phase HPLC. The column (Micro Pack MCH-10) (30 cm X 4 mm) was eluted using the solvent mixture:acetonitrile:glacial acetic acid:water (23:0.1:76.9v/v/v). Preincubation of the aortae with the sulfonyl ureas (15 microM) enhanced PGI2 release. The control release (measured as 6-oxo-PGF1 alpha) was 1.15 +/- 0.1 ng/mg wet weight. This was significantly increased to 2.30 +/- 0.20, 2.50 +/- 0.30, 2.90 +/- 0.25, 2.10 +/- 0.20 and 2.40 +/- 0.30 ng/mg by glibenclamide, gliclazide, acetohexamide, glibornuride and chlorpropamide, respectively (P less than 0.01, n = 6). Mepacrine (0.5 mM) abolished both basal and stimulated release. Thus, the enhanced PGI2 release may probably involve activation of the enzyme phospholipase A2. None of the compounds affected ADP-induced rat platelet aggregation even when the platelets were preincubated for 10 min at a concentration of 100-180 microM. The enhanced release of PGI2 may help to delay the development and progression of retinopathy, nephropathy, hypertension and thrombosis in diabetic patients prone to these diseases. Furthermore, the enhanced PGI2 release may partly underly some of the previously observed and poorly explained findings following the administration of some sulfonyl ureas into mammals.
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism*; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013453:Sulfonylurea Compounds / Q000494:pharmacology*
D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D015121:6-Ketoprostaglandin F1 alpha; D000244:Adenosine Diphosphate; D011464:Epoprostenol; D005905:Glyburide