The
neuropeptide pituitary adenylate cyclase activating polypeptide (
PACAP) and its receptors are widely expressed in the nervous system and various other tissues.
PACAP exerts strong anti-apoptotic effects in neuronal cell lines and, according to recent data, also in non-neuronal cells. The
peptide is present in the cardiovascular system and has various distinct effects. We have demonstrated earlier that
PACAP has protective effects against in vitro
ischemia/reperfusion-induced apoptosis in cardiomyocytes. Preconditioning with brief intermittent periods of
ischemia is known to provide protection against ischemic injury. The aim of the present study was to investigate whether
PACAP could enhance the protective effect of preconditioning against in vitro ischemic injury. Cultured cardiomyocytes were exposed to brief preconditioning
ischemia followed by 2 h
ischemia and 4 h reperfusion. Both
PACAP treatment and preconditioning alone significantly increased cell viability and decreased the ratio of cell death. Pretreatment with
PACAP was found to further reduce the level of cleaved
caspase-8 but it did not lead to additional survival rate when compared to cells treated with
PACAP or preconditioning alone. These results show that although both
PACAP and preconditioning have a protective effect against
ischemia/reperfusion-induced cardiomyocyte apoptosis, their effects are not additive.