Arachidonic acid metabolites regulate the secretion of atrial natriuretic peptide in cultured rat atrial cardiocytes.
Prostaglandins F2 alpha and E2 increase release of immunoreactive (irANP) in primary cultures of rat atrial cardiocytes. This effect is independent of cell density in the cultures and does not appear to operate through a cAMP-dependent mechanism. Studies that probed the PGF2 alpha effect with a number of different pharmacological antagonists suggest that it is tied to a calmodulin-dependent step. This latter effect does not appear to be related to increased calcium entry through voltage-gated channels in the plasma membrane nor to mobilization of ryanodine-sensitive intracellular calcium pools. Inhibitors of the lipoxygenase pathway, a second avenue of arachidonate metabolism, resulted in a decrease in irANP release from cultured atrial or ventricular cardiocytes. Leukotriene C4, a lipoxygenase product, had a modest effect to promote irANP release over a 24-h period. However, pretreatment of anesthetized rats with nordihydroguarietic acid, a lipoxygenase inhibitor, had no effect on stretch-dependent release of irANP from the heart in vivo. These findings suggest that the prostaglandins represent the more important group of arachidonate metabolites in regulating irANP release physiologically.
Kovacic-Milivojevic
B
B
Metabolic Research Unit, University of California, San Francisco 94143.
Schultz
H D
HD
Gardner
D G
DG
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001095:Arachidonic Acids / Q000502:physiology*; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D002478:Cells, Cultured; D015237:Dinoprost / Q000494:pharmacology; D011464:Epoprostenol / Q000502:physiology; D005260:Female; D006325:Heart Atria; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000494:pharmacology
D001095:Arachidonic Acids; D016859:Lipoxygenase Inhibitors; D011453:Prostaglandins; D013189:SRS-A; D009637:Masoprocol; D009320:Atrial Natriuretic Factor; D015237:Dinoprost; D011464:Epoprostenol; D015056:1-Methyl-3-isobutylxanthine