The role of endogenous angiotensin II in ischaemia, reperfusion and preconditioning of the isolated rat heart.

We examined the possibility that endogenous angiotensin II (AII) is involved in the regulation of the cardiac Na(+)/H(+) exchanger (NHE1) during ischaemia, reperfusion and preconditioning. Mechanical function and intracellular sodium ([Na(+)](i)) were studied in isolated, perfused rat hearts. To test whether AII production might underlie the increased activity of NHE1 on reperfusion, we applied the AII receptor antagonist losartan during ischaemia and reperfusion. Losartan significantly improved mechanical performance on reperfusion and reduced the peak [Na(+)](i) on reperfusion. It has been proposed that preconditioning inhibits the activity of NHE1 in early reperfusion. To test whether this might be because of impaired action of AII on NHE1 we applied AII throughout ischaemia and reperfusion in preconditioned hearts. AII abolished the improved mechanical recovery caused by preconditioning and the peak [Na(+)](i) on reperfusion was similar to that after ischaemia alone. Addition of the NHE1 antagonist cariporide or losartan simultaneously with AII, reversed the deleterious effects of AII on the preconditioned heart. These studies suggest that AII contributes to the activation of NHE1 in early reperfusion and that part of the beneficial effect of preconditioning may be attributed to the abolition of AII-induced activation of NHE1.