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Background
Our aim was to: 1) investigate the role of α and β-receptors in control of contractile activity in rat circular jejunal muscle; 2) explore changes in adrenergic neurotransmission via these receptors during postoperative ileus (POI); 3) determine if these changes are paralleled by intramural inflammation and delayed intestinal transit.
Methods
Muscle strips (n=8/rat) from 6 male Sprague Dawley rats per group were studied in organ chambers. Groups: Naïve controls (NC), sham controls (SC) 24h after laparotomy, rats 12h (P12h), 1 (P1d), 3 (P3d), and 7days (P7d) after laparotomy and standardized small bowel manipulation to induce POI. After spontaneous contractile activity (g/mm2/min) was recorded, dose-response curves for phenylephrine (αa; α-agonist; 10-8-3x10-6M) and isoprenaline (βa; β-agonist; 3x10-10-10-7M) were established. Responses were repeated with tetrodotoxin (TTX; blocking enteric nerves; 10-6M), after precontraction with bethanechol (3x10-6M), and with phentolamine (α-anatagonist; 10-5M), or propranolol (β-antagonist; 5x10-6M). Intestinal transit was studied by charcoal transit (% of small bowel passed). Histology of jejunal whole mounts was performed for myeloperoxidase positive cells (MPO), macrophages, and mastcells (cells/mm2).Data: mean±SEM.
Results
Spontaneous contractile activity was increased in SC, P12h, and P7d (NC 1.3±0.3; SC 3.7±0.9; P12h 4.5±1.5; P7d 3.6±1.0; p<0.05), but not in P1d (1.7±0.4) and P3d (1.8±0.5; p=NS). αa and βa inhibited spontaneous contractile activity dose-dependently in all groups (p<0.05). In NC, TTX reduced αa-induced inhibition (p<0.05), but TTX had no effect on αa-responses in POI groups (p=NS). In contrast, TTX did not affect βa-response in NC (p=NS), but increased responses in POI groups (p<0.05). αa and βa-induced inhibition was reduced in P12h, P3d, and P7d and in all POI groups, respectively (p<0.05). Precontraction had no effect on αa and βa-responses (p=NS). Effects of αa and βa were blocked by phentolamine or propranolol (p<0.05). Intestinal transit was delayed in all POI animals and recovered over time (NC 53±3; P12h 22±2; P7d 44±2%; p<0.05), but was unaffected in SC (50±5%; p=NS). MPO positive cells and mastcells increased postoperatively and peaked in P1d (NC 14±2; P1d 763±48) and P12h (NC 9±1; P12h 700±79; both p<0.05), respectively; no effect was observed in SC (56±37 and 30±12, respectively; p=NS). Macrophages peaked in P3d (NC 367±41; P3d 1306±178; p<0.05); counts in SC and P12h were similar to NC (SC 395±82; P12h 706±19; p=NS).
Conclusion
Contractile activity can be inhibited predominantly via muscular α- and β-receptors. However, during POI long lasting changes in balance of muscular and neuronal α- and β-receptors occur that might participate in pathophysiology of POI. These changes are paralleled by intramural inflammation and impaired intestinal transit. DFG KA 2329/5-1