OBJECTIVE

To investigate the mechanism of protection of reperfused ischemic heart by valsartan.

METHODS

The hearts of 40 SD rats were isolated, linked to Langendorff perfusion apparatus, and randomly divided into 5 equal groups: control group, to be perfused with modified Kreb-Henseleit (K-H) buffer for 110 minutes; ischemia/reperfusion (I/R) group, to be perfused with K-H buffer for 20 min, exposed to ischemia for 30 min, and then reperfused with K-H buffer for 60 min; HOE140 group, to be perfused with K-H buffer with HOE140, a bradykinin beta(2) receptor antagonist for 20 min, exposed to ischemia for 30 min, and then reperfused with K-H buffer with HOE140for 60 min; valsartan group, perfused with K-H buffer with valsartan for 20 min, exposed to ischemia for 30 min, and then reperfused with K-H buffer with valsartan for 60 min; and valsartan + HOE140 group, perfused with K-H buffer with valsartan + HOE140 for 20 min, exposed to ischemia for 30 min, and then reperfused with K-H buffer with valsartan + HOE140 for 60 min. The left ventricular systolic pressure (LVSP) and maximal uprising velocity of left ventricular pressure (+dp/dt(max)) were measured 20 minutes after the stabilization of perfusion, and 20, 40, and 60 minutes after reperfusion. After the stop of reperfusion Evans blue was infused via the aorta and the no-flow area was measured. The MB isoenzyme of creatine kinase (CK-MB) in the effluent liquid from the heart was measured 20 minutes after the stabilization of perfusion, and 1, 30, and 60 minutes after reperfusion.

RESULTS

The LVSP and +dp/dt(max) of the control group were significantly higher than the other 4 groups (all P < 0.01). The LVSP and +dp/dt(max) of the valsartan group were significantly higher than those of the I/R group (both P < 0.01). The LVSP and +dp/dtmax of the valsartan + HOE140 group were significantly lower than those of the valsartan group (P < 0.01 and P < 0.05). The no-flow area of the HOE140 group was not significantly different from that of the I/R group (P > 0.05). The no-flow area of the valsartan group was significantly smaller than that of the I/R group, almost half of that of the latter (P < 0.01). The CK-MB levels after I/R at different time points were all significantly higher than that of the control group (all P < 0.01). The CK-MB levels of the HOE140 group were not significantly different from those of the I/R group (all P > 0.05). The CK-MB levels at different time-pints of the valsartan group were all significantly lower than those of the I/R group (all P < 0.01). The CK-MB levels at different time-pints of reperfusion of the valsartan + HOE140 group were all significantly higher than those of the valsartan group (all P < 0.05). Linear correlation analysis showed that the CK-MB level 60 minutes after reperfusion was positively correlated with the no-flow area with a correlation coefficient of 0.85 (P < 0.01).

CONCLUSION

Valsartan protects the heart from I/R injury partially by increasing the level of bradykinin. Bradykinin beta(2) receptor antagonist blunts the cardioprotective effect of valsartan.