Abstract

We investigated the mechanism of arachidonate- and prostaglandin-induced alteration of cardiac contractile activity in isolated rat left ventricular papillary muscles. Superfusion with 10(-6) to 10(-4) M arachidonic acid resulted in a slow developing positive inotropic effect (PIE) in a concentration-dependent manner. The PIE was abolished by pretreatment with 10(-5) M indomethacin. Prostaglandin (PG) F2 alpha also produced a significant PIE in a concentration-dependent manner, but the EC50 value was approximately 2 orders of magnitude lower and the maximum contractile response was 2-fold higher than those of arachidonate. PGE2 and PGI2 were without an effect on contractile force at concentrations ranging from 10(-9) to 10(-6) M. Both arachidonate and PGF2 alpha provoked slow responses in the partially depolarized muscles in a time course similar to that of development in the PIE. Neither arachidonate nor PGF2 alpha affected tissue levels of cyclic AMP and cyclic GMP, but these molecules increased accumulations of [3H]inositol phosphates (IPs) in a concentration-dependent manner similar to that observed for their PIE. The enhanced accumulation of [3H]IPs induced by arachidonate was abolished by pretreatment with 10(-5) M indomethacin. Although an increase in [3H]IP level was relatively rapid in PGF2 alpha-treated tissues, maximum accumulations of [3H]IPs were identical between arachidonate- and PGF2 alpha-treated tissues. Thus, for comparable increases in [3H]IPs, there was a greater PIE with PGF2 alpha than with arachidonate.(ABSTRACT TRUNCATED AT 250 WORDS)