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Cardiovascular research

Effect of ischaemia and role of eicosanoids in release of atrial natriuretic factor from rat heart.


PMID 8287433

Abstract

The aim was to investigate (1) the relationship between atrial natriuretic factor (ANF) release and the extent of ischaemia-hypoxia, and (2) the potential role of eicosanoids in ANF release during global ischaemia, particularly the cyclo-oxygenase derivatives (prostaglandins) and the lipoxygenase derivatives (leukotrienes). Using an isolated perfused, spontaneously beating rat heart, global ischaemia was achieved by the reduction of perfusion flow rate relative to basal flow rate. ANF was measured by radioimmunoassay. A decrease 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 release 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 125.6(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 no 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 using a reduction of 55-60% in perfusion flow rate but with the addition to the perfusion medium of the specific cyclo-oxygenase inhibitor meclofenamate 10 microM (n = 5) or the lipoxygenase inhibitor nordihydroguaiaretic acid 10 microM (n = 5), no increase in ANF release occurred during the period of global ischaemia. Neither inhibitor affected ANF release during basal perfusion rates (7-9 ml.min-1.g-1 heart). 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 important paracrine/autacoid regulatory roles for the protection of the heart during ischaemia by stimulating ANF release, with the subsequent beneficial effects of the peptide on peripheral tissues, ultimately leading to a reduction in load on the heart.

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