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Effect of chronic renal failure on foregut smooth muscle reactivity: an experimental study
Firuzan Yildiz1, Melih Tugay, Tijen Utkan
1Department of Pharmacology, Kocaeli Medical School, Kocaeli, Turkey.
Purpose:
An association between chronic renal failure (CRF) and gastroesophageal reflux (GER) is well known. The aim of this study was to pharmacologically characterize and investigate the possible contribution of smooth muscle reactivity pathways involving GER on the CRF rat model.
Material And Methods:
Chronic renal failure was created in Sprague-Dawley rats by 5 of 6 nephrectomy. The rats were divided into 2 groups: the CRF-induced group (CRF group) and the sham-operated group (control group). Esophageal smooth muscle strips were studied in vitro for their contractile (KCl, carbachol) and relaxant (isoproterenol, serotonin, and papaverine) response to receptor activation in the organ chambers set up. Subsequently, the in vitro lower esophageal sphincter (LES) smooth muscle study was generated by KCl, carbachol, isoproterenol, nicotine, sodium nitroprusside (SNP), and papaverine.
Results:
Compared with controls, esophageal strips taken from CRF-induced rats associated with decreased smooth muscle responses to carbachol, serotonin, and increased response to KCl. Isoproterenol- and papaverine-induced relaxant responses were not affected. Contractility of the isolated LES strips were significantly increased to KCl and carbachol in the CRF group compared with the control group. Similar relaxant responses were obtained in LES strips stimulated by isoproterenol, SNP, and papaverine in the CRF and control group. Nicotine-induced relaxant responses were decreased in the CRF group compared with the control group.
Conclusions:
Our study revealed alterations of receptor-dependent esophageal and LES smooth muscle reactivity in the CRF-induced rats. Impaired foregut smooth muscle reactivity may contribute to the development of GER-related functional abnormalities in patients with CRF.
Insights
Chronic renal failure (CRF) alters esophageal and lower esophageal sphincter (LES) smooth muscle function, potentially contributing to gastroesophageal reflux (GER) related issues in patients. This study investigated these changes in a CRF rat model.
Area of Science:
- Gastroenterology
- Nephrology
- Pharmacology
Background:
- A known association exists between chronic renal failure (CRF) and gastroesophageal reflux (GER).
- The underlying mechanisms linking CRF and GER, particularly smooth muscle function, require further elucidation.
Purpose of the Study:
- To pharmacologically characterize smooth muscle reactivity in the esophagus and lower esophageal sphincter (LES) in a rat model of CRF.
- To investigate the potential contribution of altered smooth muscle pathways to GER in CRF.
Main Methods:
- Chronic renal failure was induced in Sprague-Dawley rats via subtotal nephrectomy.
- Esophageal and LES smooth muscle strips were isolated and studied in vitro for contractile and relaxant responses to various agonists and antagonists.
- Responses were compared between CRF-induced rats and sham-operated controls.
Main Results:
- CRF rats exhibited decreased esophageal smooth muscle response to carbachol and serotonin, but increased response to KCl.
- Lower esophageal sphincter (LES) contractility was significantly increased in CRF rats.
- Nicotine-induced relaxation was reduced in the LES of CRF rats, while other relaxant responses remained unaffected.
Conclusions:
- Receptor-dependent esophageal and LES smooth muscle reactivity is altered in rats with CRF.
- Impaired foregut smooth muscle function in CRF may contribute to GER-related functional abnormalities observed in patients.
