Abstract 5263: Renin Angiotensin System Plays a Crucial Role in the Development of Myocardial Ischemia/Reperfusion Injury With a Condition of Renal Failure in Mice
Background: The clinical relationship between the heart and renal diseases has been clarified. Although renin angiotensin system (RAS) mediates the development of cardio-renal syndrome, little is known about the etiology obtained from experimental models with myocardial ischemia and renal failure.
Methods: To test the hypothesis that RAS plays a pivotal role in cardio-renal syndrome, we developed a novel murine cardio-renal disease model using both the 5/6 subtotal nephrectomy (NTX) and the myocardial ischemia/reperfusion injury (I/R) techniques. Four weeks after the subtotal nephrectomy, the left coronary artery was occluded for 60 minutes followed by 24 hour reperfusion.
Results: Serum creatinine levels on day 28 were higher in the NTX group (0.28±0.04 mg/dl, n=8) compared to those in the non-NTX group (0.13±0.01 mg/dl, n=5, p<0.05). The infarction area/area at risk ratio significantly increased in NTX+I/R mice (50.7±5.9 %, n=7) compared to the non-NTX+I/R mice (20.8±3.1 %, n=8, p<0.05), while ischemic area/whole myocardial area was comparable between the two groups. The NTX+I/R hearts had significantly larger left ventricular diameters compared with that of the non-NTX+I/R mice. The number of infiltrating cells was enhanced by the NTX+I/R, while they were limited in non-NTX+I/R. Interstitial fibrosis also increased in NTX+I/R, while non-NTX+I/R suppressed this change. The hearts isolated from NTX+I/R mice increased the mRNA expression ratios (the NTX-IR group per the native group) of angiotensin-converting enzyme (1.57±1.26) and angiotensin II receptor type 1 levels (1.21±0.07) measured by quantitative RT-PCR.
Conclusion: RAS deeply involves the development of cardio-renal syndrome and it may have a clinical usefulness in the treatment of myocardial ischemia with renal dysfunction.