ANP preconditioning does not increase protection against experimental pancreatitis, observed after general anesthesia and jugular vein catheterization.
It has been widely shown that preconditioning, inducing heat shock proteins, can protect against experimentally induced pancreatitis. Solid evidence indicates that HSP70 plays a central role in this context, possibly by inhibition of premature intracellular trypsinogen activation. Current preconditioning protocols such as whole body hyperthermia are, however, quite strenuous and clinically not applicable. There is little data on other means to induce pancreatic HSPs such as pharmacologic pretreatment.However, in models of ischemic liver reperfusion injury, it has been demonstrated that atrial natriuretic peptide (ANP) can be used for such pharmacologic preconditioning. Evidence indicates that ANP exerts its protective effects via increased cGMP levels, activation of heat shock transcription factor (HSF) and, increased protein levels of HSP70. Pancreatic acinar cells express ANP receptors and respond to ANP treatment with increased cGMP levels. We have, therefore, investigated whether intravenous ANP pretreatment could be used to protect the pancreas against experimental pancreatitis. When given 20 minutes prior to pancreatitis induction, ANP pretreatment had no effect on cerulein-induced pancreatitis. In contrast, 24 hours after preconditioning, induction of HSP70 protein expression and protection against experimental pancreatitis were found. However, controls treated with NaCl without ANP showed a similar response. This indicates that stress caused by general anesthesia and jugular vein catheterization can be sufficient for preconditioning while ANP, in contrast to models of ischemic liver reperfusion injury, does not confer additional protection.
Ploessl
I
I
Department of Medicine II, Grosshadern Hospital, University of Munich, Institute of Pathology, University of Munich, Germany.
Gallmeier
E
E
Schaefer
C
C
Bilzer
M
M
Bittmann
I
I
Göke
B
B
Wagner
A C C
AC
D000768:Anesthesia, General; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000627:therapeutic use*; D001794:Blood Pressure; D002406:Catheterization, Peripheral; D006152:Cyclic GMP; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D007601:Jugular Veins; D008297:Male; D010179:Pancreas / Q000166:cytology / Q000378:metabolism; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018840:HSP70 Heat-Shock Proteins; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP