Cumulative effects of AT1 and AT2 receptor blockade on ischaemia-reperfusion recovery in rat hearts

Though ischaemia/reperfusion injury induces renin-angiotensin systemic (RAS) activation and increased heart angiotensin production, the effects of blockade of the two main angiotensin 11 receptors, AT, and AT2, are not definitively established. Using a Langendorff heart preparation, effects of Valsartan 10' M (AT, receptor blocker), PD 123319 10-7 M (AT2 receptor blocker) or both in the presence of a controlled concentration of angiotensin 11 (10-8 M) in order to reproduce systemic RAS activation were studied in adult male Wistar rat heartssubmitted to ischaemia/reperfusion. Ischaemia/reperfusion impaired both systolic and diastolic function through a no-reflow phenomenon. Presence of a controlled concentration of angiotensin in the perfusate, enough to produce a significant AT, -induced vasoconstriction before ischaernia, has no relevant influence on ischaemia/reperfusion injury. Only blockade of both AT, and AT2 receptors significantly improved recovery from ischaemia; better ventricle function paralleled better perfusion. The results suggest that blockade of angiotensin 11 receptors is cumulative since blockade of AT, and AT2 receptors is more effective than blockade of just one of them. 0 2005 Elsevier Ltd. All rights reserved.