Pituitary adenylate cyclase activating polypeptide (
PACAP) is a
neuropeptide with well-known cytoprotective effects. 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. PACAP⁻/⁻ mice underwent 45 or 60 min 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, Bowmann'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. 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. In conclusion, the lack of endogenous
PACAP leads to higher susceptibility to in vivo renal
ischemia/reperfusion, suggesting that
PACAP has an endogenous renoprotective effect.