gastrin-releasing-peptide and Ischemia

We investigated the effect of gastrin-releasing peptide (GRP) and its antagonist RC-3095 on intestinal microcirculation after ischemia-reperfusion. Intestinal ischemia was induced in female Wistar rats by occlusion of the superior mesenteric artery for 40 min. Ten minutes prior to reperfusion, infusion of GRP or RC-3095 was started. A jejunal segment was exteriorized and the microhemodynamics of the mucosa and submucosa were examined by intravital microscopy and compared both with normal and ischemic controls (without application of the regulatory peptide). Ischemia-reperfusion significantly decreased functional capillary density from 891.2 +/- 14.1 to 398.3 +/- 11.4 cm(-1). Capillary red blood cell velocity was reduced from 0.46 +/- 0.01 to 0.37 +/- 0.01 mm/s (p < 0.05). Furthermore, both sticking and rolling of leukocytes were enhanced. 3.4 +/- 1.1% of the villi were not perfused at all. GRP infusion reversed the microcirculatory ischemia-reperfusion injury by increasing functional capillary density to 669.8 +/- 8.3 cm(-1) and red blood cell velocity to 0.62 +/- 0.01 mm/s (p < 0.05). In addition, application of GRP resulted in a complete absence of stasis (0%) in the villi. Leukocyte-endothelium adherence remained unchanged when compared to the ischemic controls. In contrast, application of RC-3095 caused an aggravation of microcirculatory disturbances demonstrated by a markedly increased number of non-perfused villi (42.5 +/- 4.2%; p < 0.05 vs. ischemic controls) and a significantly reduced functional capillary density (346.2 +/- 8.4 cm(-1), p < 0.05 vs. ischemic controls). In addition, RC-3095 led to an increased permanent leukocyte adherence in postcapillary venules whereas rolling was significantly reduced when compared to normal controls. We conclude that GRP in pharmacological doses has a protective effect on intestinal microcirculation during reperfusion. Furthermore, these data suggest that endogenous GRP may play a decisive role in the maintenance of microvascular integrity during reperfusion.

Topics: Analysis of Variance; Animals; Antineoplastic Agents; Bombesin; Female; Gastrin-Releasing Peptide; Injections, Intravenous; Intestines; Ischemia; Microcirculation; Microscopy, Fluorescence; Peptide Fragments; Rats; Rats, Wistar; Reperfusion Injury

With the use of intravital fluorescence microscopy we demonstrate, that GRP in pharmacological doses reduces ischemia/reperfusion injury in the rat. As mechanism we discuss a precapillary vasodilation that has a protective effect on the capillary system downstream. A direct influence on leukocyte-endothelium interaction in post-capillary venules could not be shown. In addition, we show that even the GRP endogenously released plays an important role for the regulation of microvascular perfusion after ischemia/reperfusion injury.

Topics: Animals; Blood Flow Velocity; Bombesin; Gastrin-Releasing Peptide; Intestine, Small; Ischemia; Microcirculation; Peptide Fragments; Rats; Rats, Wistar; Reperfusion Injury