Impact of Gastrin-Releasing Peptide on Intestinal Microcirculation after Ischemia-Reperfusion in Rats

Abstract

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.

Oxidative state in intestine and liver after partial hepatectomy in rats. Effect of bombesin and neurotensin

“…An alternative explanation might be the reduction of endotoxemia, which is associated with generation of oxygen free radicals via a xanthine oxidase-dependent pathway [43]. Moreover, improvement of intestinal and liver microcirculation by regulatory peptides [44] prevents hypoxia and energy depletion that leads to oxidative metabolism.…”

Vasoactive Intestinal Polypeptide and Gastrin-Releasing Peptide Attenuate Hepatic Microvasculatory Disturbances following Intestinal Ischemia and Reperfusion

“…Heuser et al [26]could show that GRP in pharmacological doses has a protective effect on intestinal microcirculation during reperfusion. Further investigations with the GRP antagonist RC-3095 suggested that endogenous GRP may play a decisive role in the maintenance of microvascular integrity during reperfusion.…”

Pleiotropic effects of bombesin and neurotensin on intestinal mucosa: Not just trefoil peptides

“…Up to now, numerous experimental studies have demonstrated the protective effect of BBS and NTS against diverse types of intestinal injury, such as administration of elemental diets or methotrexate, induction of chemical colitis, burns, radiation therapy, ischemia/reperfusion and small bowel resection [3][4][5][6][7][8][9] . However, the molecular and cellular mechanisms implicated in their intestinal mucosa-healing effect remained unresolved for a long period.…”