Role of calcitonin gene related peptide in the modulation of intestinal circulatory, metabolic, and myoelectric activity during ischemia/reperfusion.
Calcitonin gene related peptide (CGRP) is widely distributed in the myenteric neurons along GI tract. Biological effects of CGRP on gastrointestinal tract include increase in the intestinal blood flow, relaxation of the smoth muscle and slight increase in the slow wave amplitude (SWA) with no effect on frequency (SWF) of intestinal myoelectric activity (IMA). The aim of this study was to evaluate the possible protective effects of endo- and exogenous CGRP against ischemia/reperfusion (I/R) induced bowel injury in rats. Experiments were performed on 30 fasted anesthetized Wistar rats. Systemic arterial blood pressure (AP), mesenteric blood flow (MBF) and microcirculatory intestinal blood flow (LDBF) were measured. Oxygen consumption (VO2) was estimated from MBF and mesenteric AVO2 difference. IMA was recorded by 4 monopolar electrodes in proximal jejunum and analyzed using computer program with Fourrier analysis of SWF. Control ischemia induced by 30 min total occlusion of anterior mesenteric artery (AMA) reduced SWA by 25+/-5% and SWF by 24+/-4%. At the end of 60 minute reperfusion period SWA and SWF values were restored to control values but SWF showed instability. At the 15th minute of reperfusion period MBF, LDBF and VO2 increased to 109+/-6, 119+/-11 and 120+/-7% of control values respectively. Infusion of exogenous CGRP (0,16 microg/kg/min i.a.) increased MBF, LDBF and VO2 by 26+/-6, 31+/-9 and 20+/-4% respectively in comparison to control values. In the same experimental group SWA increase of 14% was observed with not significant changes in SWF. In the group where CGRP was administrated before and during 30 min period of intestinal ischemia MBF, LDBF and VO2 values at 15th minute of reperfusion were significantly higher by 24+/-6, 32+/-7 and 17+/-5% respectively in comparison to the values observed in the control reperfusion. In that group SWA values were restored to preocclusion values at 15th minute of reperfusion yet and SWF showed much more stability. Infusion of CGRP receptor antagonist (CGRP 8-37) reduced MBF, LDBF and VO2 by 12+/-7, 14+/-8 and 11+/-6% respectively (differences not significant versus control). In I/R group when CGRP 8-37 was given hemodynamic parameters (during reperfusion) were significantly lower and IMA parameters were not restored to preocclusion values. We conclude, that endogenous and exogenous CGRP attenuate circulatory parameters of the small intestine during ischemia and reperfusion. A direct correlation exists between hemodynamic, metabolic and myoelectric effects of CGRP.
Pawlik
W W
WW
Department of Physiology, Jagiellonian University Faculty of Medicine, Cracow, Poland.
Obuchowicz
R
R
Biernat
J
J
Sendur
R
R
Jaworek
J
J
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology* / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000098:blood supply* / Q000503:physiopathology*; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D016065:Myoelectric Complex, Migrating / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D015427:Reperfusion Injury / Q000503:physiopathology*; D013152:Splanchnic Circulation / Q000187:drug effects / Q000502:physiology
D020011:Protective Agents; D015740:Calcitonin Gene-Related Peptide