Comparison of the effects of milrinone and OPC 3911 with those of isoprenaline, forskolin and dibutyryl-cAMP in rat aorta

Abstract

1. OPC 3911 and milrinone, inhibitors of a cyclic nucleotide phosphodiesterase, and isoprenaline were more potent against contractions induced by phenylephrine (1 microM) than by K+ (60 mM). A similar tendency was found for dibutyryl-cAMP (db-cAMP) and forskolin, while the opposite was evident for nifedipine and diltiazem. 2. Contractions induced by Bay K 8644 (0.1 microM), in the presence of K+ (12 mM), were abolished by OPC 3911 (10 microM), milrinone (10 microM), db-cAMP (100 microM) and forskolin (1 microM). These agents had little effect on contractions induced by Bay K 8644 in the presence of K+ (20 mM), whereas diltiazem (10 microM) caused complete inhibition. 3. In nominally Ca(2+)-free medium, OPC 3911 (10 microM), milrinone (10 microM), db-cAMP (100 microM) and forskolin (1 microM) reduced phenylephrine-induced contractions. Db-cAMP and forskolin also attenuated contractions elicited by caffeine (20 mM). 4. Pretreatment by ryanodine (10 microM) reduced the effects of OPC 3911 (10 microM), milrinone (10 microM) and forskolin (1 microM) on phenylephrine-induced contractions.