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Acta Physiologica 2011; Volume 202, Supplement 684
The Joint Conference (FAMÉ 2011) of the LXXVth Meeting of the Hungarian Physiological Society, XVIth Meeting of the Hungarian Society of Anatomists, Experimental Section of the Hungarian Society for Experimental and Clinical Pharmacology and Hungarian Society for Microcirculation and Vascular Biology
6/8/2011-6/11/2011
Pécs, Hungary
MICE DEFICIENT IN PITUITARY ADENYLATE CYCLASE ACTIVATING POLYPEPTIDE (PACAP) SHOW INCREASED SUSCEPTIBILITY TO IN VIVO RENAL ISCHEMIA/REPERFUSION INJURY
Abstract number: P30
Horvath1 G., Szakaly2 P., Laszlo1 E., Kovacs3 K., Racz3 B., Ferencz4 A., Lubics1 A., Kiss1 P., Tamas1 A., Brubel1 R., Opper1 B., Baba5 A., Hashimoto5 H., Farkas1 J., Matkovits1 A., Magyarlaki6 T., Helyes7 Zs., Reglodi1 D.
Aims:
We have reported earlier that PACAP decreases mortality and the degree of tubular atrophy in a rat model of renal ischemia/reperfusion injury. Recently, we have shown that kidney cultures isolated from PACAP deficient mice show increased susceptibility to renal oxidative stress. Based on these previous studies, we raised the question whether PACAP deficient mice display increased sensitivity to in vivo kidney ischemia/reperfusion.
Methods:
PACAP -/- mice underwent 45 or 60 minutes of renal ischemia followed by 2 weeks reperfusion. Kidneys were processed for histological analysis. Sections stained with PAS-haematoxylin were graded for the following parameters: degree of tubular dilation, Bowman's capsule dilation, lymphocyte and macrophage infiltration, thyroidization and the disappearance of the PAS-positive glycocalyx from under the brush border. In other sets of experiments, tissue cytokine expression and the level of the endogenous antioxidant superoxide dismutase (SOD) were also determined after 60 min ischemia/reperfusion.
Results:
Our results show that while intact kidneys were not different between wild-type and PACAP deficient mice, marked differences were observed in the histological structures in groups that underwent ischemia/reperfusion. PACAP deficient mice had a worse histological outcome, with significantly higher histological scores for all tested parameters. Cytokine expression was also markedly different between wild-type and PACAP deficient mice. In addition, the level of SOD was significantly lower in PACAP -/- animals after ischemia/reperfusion.
Conclusion:
The lack of endogenous PACAP leads to higher susceptibility to in vivo renal ischemia/reperfusion, suggesting that PACAP has an endogenous renoprotective effect.
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Acta Physiologica 2011; Volume 202, Supplement 684 :P30