缺血的影响及类二十烷酸在大鼠心脏心房利钠因子释放中的作用。

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

作者信息

Chen B N, Rayner T E, Menadue M F, McLennan P L, Oliver J R

机构信息

Department of Medicine, Flinders Medical Centre, Bedford Park, Australia.

出版信息

Cardiovasc Res. 1993 Sep;27(9):1576-9. doi: 10.1093/cvr/27.9.1576.

DOI:10.1093/cvr/27.9.1576

PMID:8287433

Abstract

OBJECTIVE

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).

METHODS

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.

RESULTS

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).

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 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.

摘要

目的

本研究旨在探讨（1）心房利钠因子（ANF）释放与缺血缺氧程度之间的关系，以及（2）类花生酸在全心缺血期间ANF释放中的潜在作用，特别是环氧化酶衍生物（前列腺素）和脂氧化酶衍生物（白三烯）。

方法

使用离体灌注、自发搏动的大鼠心脏，通过相对于基础流速降低灌注流速来实现全心缺血。采用放射免疫分析法测定ANF。

结果

灌注流速降低75 - 80%，最终值达到2 - 2.5 ml·min⁻¹·g⁻¹心脏（n = 6），导致ANF释放逐渐但持续增加，12分钟后达到平台期，相对于基线达到峰值89.9（标准误26.6）%。灌注流速降低55 - 60%（n = 5）也导致ANF分泌增加，在14分钟时相对于基线峰值为125.6(23.2)%。灌注流速降低25 - 30%，最终值达到5 - 6.75 ml·min⁻¹·g⁻¹心脏（n = 4），ANF释放无变化。ANF释放的平均基础值为8.23(2.39) ng·min⁻¹·g⁻¹心脏（n = 26）。在另一系列实验中，灌注流速降低55 - 60%，但在灌注介质中添加10 μM特异性环氧化酶抑制剂甲氯芬那酸（n = 5）或10 μM脂氧化酶抑制剂去甲二氢愈创木酸（n = 5），在全心缺血期间ANF释放未增加。两种抑制剂在基础灌注流速（7 - 9 ml·min⁻¹·g⁻¹心脏）期间均不影响ANF释放。