MDL 27,032 relaxes vascular smooth muscle and inhibits protein kinase C.

The smooth muscle relaxant effect of MDL 27,032, 4-propyl-5-(4-pyridinyl)-2(3H)-oxazolone, was studied in vitro using strips of femoral arteries and saphenous veins from dogs and trachea from guinea pigs. MDL 27,032 (10 −6 −10 −3 M) produced a concentration-dependent relaxation of arterial and venous strips contracted by both phenylephrine and KCl as well as trachea contracted by carbachol. MDL 27,032 also antagonized contractions of arterial and venous strips produced by phorbol 12,13-dibutyrate (PDB), a protein kinase C activator, both in normal-Ca 2+ and zero-Ca 2+ medium. The compound inhibited protein kinase C in soluble extracts prepared from saphenous veins of dogs, with an IC 50 value of 36;6 μM. MDL 27,032 was more effective against the contractions produced by phenylephrine and serotonin than by KCl in arteries, but no such selectivity was noted in veins