Atrial natriuretic factor protects the isolated working ischaemic rat heart against the action of angiotensin II

The interaction between atrial natriuretic factor [synthetic human ANF-(103–126)] and angiotensin II (Ang II) and its influence on reperfusion arrhythmias, cardiodynamics, enzyme loss and metabolic changes were investigated in isolated ischaemic working rat hearts. Acute regional myocardial ischaemia was induced by coronary artery occlusion which was associated with ventricular fibrillation. Perfusion with 1 x 10-9 mol/l Ang II markedly aggravated these arrhythmias. Perfusion with 1 x 107 mol/l ANF, in contrast, gave protection against ventricular fibrillation and prevented Ang II-induced aggravation of ventricular fibrillation. Atrial natriuretic factor improved cardiodynamics, in particular, during reperfusion, whereas Ang II impaired cardiodynamics and increased the release of creatine kinase and lactate dehydrogenase. These adverse effects of Ang II were absent when ANF was simultaneously perfused. Compared with control hearts, myocardial tissue levels of glycogen, ATP and creatine phosphate were increased in hearts perfused with either ANF or ANF plus Ang II, whereas lactate levels decreased. Perfusion with Ang II alone led to deterioration in these metabolic parameters. These results in isolated working rat hearts suggest that ANF protects against the consequences of ischaemia and reperfusion and that functional antagonism between ANF and Ang II may contribute to this.