Positive inotropic effect and phosphoinositide breakdown mediated by arachidonic acid and prostaglandin F2 alpha.
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)
Otani
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Department of Surgery, University of Connecticut School of Medicine, Farmington.
Otani
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Das
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DK
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009712:Nucleotides, Cyclic / Q000032:analysis; D010210:Papillary Muscles / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical
D001095:Arachidonic Acids; D009712:Nucleotides, Cyclic; D010716:Phosphatidylinositols; D016718:Arachidonic Acid; D015237:Dinoprost; D011493:Protein Kinase C; D002118:Calcium