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

The angiotensin II type 1 receptor (AT(1)R) antagonist protects the heart against acute ischaemia-reperfusion injury. The underlying mechanism is unclear.To determine the effects of angiotensin II type 1 receptor blockade, valsartan on AT(1) and AT(2) 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 left ventricular systolic pressure, maximal uprising velocity of left ventricular pressure (+dp/dt(max)), maximal decreasing velocity of left ventricular pressure (-dp/dt(max)) and coronary flow were measured after stabilization of the perfusion. The isoenzyme of creatine kinase in the effluent liquid from the heart, AT(1) and AT(2) 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/dt(max) and -dp/dt(max), indicating severe cardiac dysfunction and decreased coronary effluence. Concurrently, myocardial AT(1) and AT (2) receptor mRNA and protein expression were increased with valsartan. However, AT(2) receptor mRNA and protein expression decreased during ischaemia-reperfusion. The creatine kinase levels at different time points of the valsartan group were significantly lower. The results suggested that valsartan improved left ventricular function and increased coronary effluence because the angiotensin receptor blocker valsartan induced cardioprotection associated with upregulating AT(2) receptor protein and mRNA expression after ischaemia-reperfusion in isolated rats.