EFFECT OF ISCHEMIA AND ROLE OF EICOSANOIDS IN RELEASE OF ATRIAL-NATRIURETIC-FACTOR FROM RAT-HEART

Objective: The aim was to investigate (1) the relationship between atr ial natriuretic factor (ANF) release and the extent of ischaemia-hypox ia, and (2) the potential role of eicosanoids in ANF release during gl obal ischaemia, particularly the cyclo-oxygenase derivatives (prostagl andins) and the lipoxygenase derivatives (leukotrienes). Methods: Usin g an isolated perfused, spontaneously beating rat heart, global ischae mia was achieved by the reduction of perfusion flow rate relative to b asal flow rate. ANF was measured by radioimmunoassay. Results: A decre ase in perfusion flow rate by 75-80% to a final value of 2-2.5 ml.min- 1.g-1 heart (n=6) caused a gradual but sustained increase of ANF relea se which reached a plateau after 12 min, attaining a peak value of 89. 9(SEM 26.6)% over baseline. A decrease in perfusion flow rate by 55-60 % (n=5) also resulted in an increased ANF secretion, with a peak of 12 5.6(23.2)% over baseline at 14 min. A decrease in perfusion flow rate by 25-30% to a final value of 5-6.75 ml.min-1.g-1 heart (n=4) showed n o change in ANF release. The mean basal value of ANF release was 8.23( 2.39) ng.min-1.g-1 heart (n=26). In a separate series of experiments u sing a reduction of 55-60% in perfusion flow rate but with the additio n to the perfusion medium of the specific cyclo-oxygenase inhibitor me clofenamate 10 muM (n=5) or the lipoxygenase inhibitor nordihydroguaia retic acid 10 muM (n=5), no increase in ANF release occurred during th e period of global ischaemia. Neither inhibitor affected ANF release d uring basal perfusion rates (7-9 ml.min-1.g-1 heart). Conclusions: ANF released in response to global ischaemia is likely to be mediated by prostanoids generated via the cyclo-oxygenase pathway and leukotrienes generated via the lipoxygenase pathway. Both pathways may provide imp ortant paracrine/autacoid regulatory roles for the protection of the h eart during ischaemia by stimulating ANF release, with the subsequent beneficial effects of the peptide on peripheral tissues, ultimately le ading to a reduction in load on the heart.