Valsartan-induced cardioprotection involves angiotensin II type 2 receptor upregulation in isolated ischaemia and reperfused rat hearts

Abstract

The angiotensin II type 1 receptor (AT1R) antagonist protects the heart against acute ischaemia-reperfusion injury. The underlying mechanism is unclear. To determine the eff ects of angiotensin II type 1 receptor blockade, valsartan on AT1 and AT2 receptor during ischaemia reperfusion in isolated rat, the hearts of 24 SD rats were isolated, linked to Langendorff perfusion apparatus, and exposed to ischaemia for 30 min. The l eft ventricular systolic pressure, maximal uprising velocity of left ventricular pressure (+dp/dtmax), maximal decreasing velocity of left ventricular pressure (-dp/dtmax) and coronary fl ow were measured after stabilization of the perfusion. The isoenzyme of creatine kinase in the effl uent liquid from the heart, AT1and AT2 receptor mRNA and protein expression were measured after stabilization of the perfusion. The results showed that ischaemia-reperfusion induced a marked decrease in left ventricular systolic pressure, +dp/dtmax and -dp/dtmax, indicating severe cardiac dysfunction and decreased coronary effl uence. Concurrently, myocardial AT1 and AT 2 receptor mRNA and protein expression were increased with valsartan. However, AT2 receptor mRNA and protein expression decreased during ischaemia-reperfusion. The creatine kinase levels at diff erent time points of the valsartan group were signifi cantly lower. The results suggested that valsartan improved left ventricular function and increased coronary effl uence because the angiotensin receptor blocker valsartan induced cardioprotection associated with upregulating AT2 receptor protein and mRNA expression after ischaemia-reperfusion in isolated rats.