Object To determine the effects of Angiotensin II Type 1 receptor blockade valsartan on AT1 and AT2 receptor during ischaemia reperfusion.
Methods The hearts of 24 SD rats were isolated, linked to Langedorff perfusion apparatus, and randomly divided into 3 equal groups: control group, perfused with modified Kreb-Henseleit (K-H) buffer for 110 min; ischaemia/reperfusion (I/R) group, perfused with K-H buffer for 20 min, exposed to ischaemia for 30 min, and then reperfused with K-H buffer for 60 min; valsartan group, perfused with K-H buffer with valsartan for 20 min, exposed to ischaemia for 30 min, and then reperfused with K-H with valsartan for 60 min. The left ventricular (LV) function including maximal uprising velocity of left ventricular pressure (+dp/dtmax) and maximal decreasing velocity of left ventricular pressure (–dP/dtmax) were monitor. The coronary effluent were measured 20 min after the stabilisation of perfusion, and 20, 40, and 60 min after reperfusion. After the stop of reperfusion, the structure were observed using electron microscope. The AT1 and AT2 receptor mRNA express were examined by Northern blot. The AT1 and AT2 receptor protein expression were examed by Northern blot.
Results Compared with control, I/R impaired left ventricular systolic and diastolic function (+dp/dtmax 1892±231 mm Hg.s−1 vs 836±223 mm Hg.s−1; −dp/dtmax --1175±223 mm Hg.s−1 vs −613±224 mm Hg.s−1, all p<0.01), decreased coronary effluent (5.9±0.8 ml.min−1 vs 3.3±0.5 ml.min−1, p<0.01) damaged the structure. Increased AT1 receptor mRNA and protein. Decreased AT2 receptor mRNA and protein express. valsartan improved left ventricular function (+dp/dtmax 1337±226 mm Hg.s−1; −dp/dtmax −871±208 mm Hg.s−1, compared with I/R group, all p<0.01), increased coronary effluent (4.2±∆0.7 ml.min−1, compared with I/R group, p<0.01). Increased AT2 receptor mRNA and protein express with no changes in AT1 receptor mRNA and protein express.
Conclusions AT1 receptor blockade valsartan induces short-term cardioprotection associated with enhanced AT2 receptor expression during myocardial ischaemia reperfusion.
- Valsartan, ischaemia-reperfusion, AT1 receptor
- AT2 receptor