Effect of chronic renal failure on foregut smooth muscle reactivity: an experimental study.
OBJECTIVE
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.


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.
Yildiz
Firuzan
F
Department of Pharmacology, Kocaeli Medical School, Kocaeli, Turkey.
Tugay
Melih
M
Utkan
Tijen
T
Yazir
Yusufhan
Y
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D049630:Esophageal Sphincter, Lower / Q000503:physiopathology; D004947:Esophagus / Q000187:drug effects / Q000503:physiopathology*; D005764:Gastroesophageal Reflux / Q000209:etiology / Q000503:physiopathology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007676:Kidney Failure, Chronic / Q000150:complications / Q000503:physiopathology*; D009119:Muscle Contraction; D009126:Muscle Relaxation; D009538:Nicotine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010208:Papaverine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D018679:Cholinergic Agonists; D009599:Nitroprusside; D012701:Serotonin; D011189:Potassium Chloride; D009538:Nicotine; D002217:Carbachol; D010208:Papaverine; D007545:Isoproterenol