Involvement of AQP 1 in the cardio-protective effect of remifentanil post-conditioning in ischemia/reperfusion rats

Abstract

Background: our research aim to study the role of AQP1 in the cardioprotective effect of remifentanil post-conditioning for myocardial ischemia/reperfusion injury.

Methods: Ninety Sprague-Dawley (SD) rats were divided into 6 groups: sham operation group (Sham group), myocardial ischemia and reperfusion group (I/R group), postconditioning of remifentanil group (R-post), postconditioning of remifentanil plus AQP1 inhibitor acetazolamide group (R-post +Ace), postconditioning of remifentanil plus opioid-receptor antagonist compounds (R-post +AC), postconditioning of remifentanil plus AQP1 enhancer arginine vasopressin (R-post +AV). All groups except the sham operation group were given 30 min ischemia in left anterior descending (LAD) coronary arteries. All groups were then given 120 min reperfusion to the LAD. Before reperfusion, the R-post, R-post +Ace, R-post +AC, R-post +AV groups were given 10 min remifentanil post-conditioning. Hemodynamic data were measured every 30 min after initiation of ischemia. The rats' hearts were exercised for detecting infarct size and water content in the left ventricle, and AQP1 expression were also detected.

Results: The R-post group showed a significant reduction of the infarct size compared to the I/R group. The effect of R-post for reducing infarct size was slightly enhanced by adding acetazolamide to R-post, so significant differences could still be found when compared R-post+Ace group to the I/R group. The effect of infarct size reduction brought by R-post was blocked by the opioid-receptor antagonist compounds. This effect was also blocked by the AQP1 enhancer. Similar outcomes were found considering the water content of the left ventricle and the AQP1 expression.

Conclusion: Cardioprotective effect of remifentanil post-conditioning may initiate through inhibiting the function of AQP1.

Keywords: AQP1; cardioprotective effect; remifentanil post-conditioning.

Figure 1

Protocols of remifentanil administration. Sham, sham operation group; I/R group, myocardial ischemia/reperfusion group; R-post, postconditioning of remifentanil group; R-post +Ace, postconditioning of remifentanil plus acetazolamide group; R-post +AC, postconditioning of remifentanil plus antagonist compounds; R-post +AV, postconditioning of remifentanil plus arginine vasopressin.

Figure 2

Myocardial infarct size. The images of myocardial infarct size showed that the R-post+Ace group presented the smallest ischemia size while the R-post+AV group presented with the largest size. The exact data were given in Table 2.

Figure 3

Western blot analysis. Expression of AQP1 was characterized using densitometry of western blot analysis. The expression of AQP1 was compared to β-actin and presented as AQP1/β-actin ratio. *Compared to sham group, P<0.05. †Compared to I/R group, P<0.05. ‡Compared to R-post group, P<0.05.

Figure 4

Real-time qPCR analysis. Real-time qPCR was performed to detect the expression of AQP1mRNA in the myocytes, higher AQP1mRNA indicated a higher myocardial edema. *Compared to sham group, P<0.05. †Compared to I/R group, P<0.05. ‡Compared to R-post group, P<0.05.