Importance of nitric oxide (NO) and adenosine in the mechanism of gastric preconditioning induced by short ischemia.
OBJECTIVE
Gastric mucosa subjected to repeated brief episodes of ischemia exhibits an increased resistance to damage caused by a subsequent prolonged ischemic insult and this is called gastric preconditioning. In this study, L-NNA, a non-selective NO-synthase inhibitor, and aminoguanidine, a relative inhibitor of inducible NO-synthase (iNOS), were applied prior to short ischemia (occlusion of celiac artery 1-5 times for 5 min) followed by a subsequent exposure to 0.5 h of ischemia and 3 h of reperfusion (I/R).


METHODS
Male Wistar rats were used in all studies.


RESULTS
Short ischemia reduced significantly I/R-induced lesions while raising significantly the GBF and luminal NO content. These effects were attenuated by L-NNA and aminoguanidine and restored by addition of L-arginine and SNAP to L-NNA and aminoguanidine. Pretreatment of with adenosine (10 mg/kg i.p.) significantly reduced I/R lesions and accompanying fall in the GBF induced by I/R. These protective and hyperemic effects of standard preconditioning and adenosine were significantly attenuated by pretreatment with 8-phenyl theophylline (SPT, 10 mg/kg i.g.), an antagonist of adenosine A1 and A2 receptors.


CONCLUSIONS
We conclude that gastric ischemic preconditioning is considered as one of the major protective mechanism in the stomach that involves key vasodilatory mediators such as NO and adenosine.
Brzozowski
T
T
Department of Physiology, Jagiellonian University Medical College, 16 Grzegorzecka Str., 31-531 Cracow, Poland. mpbrzozo@cyf-kr.edu.pl
Ptak
A
A
Kwiecień
S
S
Pajdo
R
R
Drozdowicz
D
D
Pawlik
M
M
Konturek
S J
SJ
Pawlik
W W
WW
D000241:Adenosine / Q000502:physiology*; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005753:Gastric Mucosa / Q000098:blood supply* / Q000502:physiology; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000241:Adenosine