Reduction of gastrointestinal motility by unilateral thyroparathyroidectomy plus subdiaphragmatic vagotomy in rats

Abstract

Aim: To investigate whether the combined methods of unilateral thyroparathyroidectomy (TPX) and subdiaphragmatic vagotomy (VAX) can be adapted for rats and used as a reliable method to produce a rat model of long-term reduction of gastrointestinal (GI) motor function.

Methods: Male Sprague-Dawley rats were randomly divided into 3 groups, normal, sham-operated and unilateral TPX plus VAX. The TPX plus VAX rats received VAX 7 d after application of TPX, and dietary intake and fecal output were then measured daily for 1 wk. After completion of the experiments, gastric emptying and small bowel transit were measured in vivo, and the contractile responses of colonic strips to excitatory and inhibitory neurotransmitters were estimated using isometric force transducers in vitro.

Results: In comparison with normal and sham-operated rats, rats which received unilateral TPX plus VAX showed a significant decrease in body weight and in fecal pellet number and weight throughout the entire week. Application of TPX plus VAX to rats markedly delayed gastric emptying and small bowel transit. In TPX plus VAX rats, the longitudinal muscles of the proximal colon showed a significant reduction in contractile responses to acetylcholine (5 × 10(-6) mol/L), and a dramatic attenuation of contractile responses was also observed in both the longitudinal and circular muscles of the distal colon. However, the spontaneous contractility of the colonic strips from TPX plus VAX rats was not significantly affected by treatment with N-nitro-L-arginine-methyl ester (0.1 mol/L).

Conclusion: The results indicate that unilateral TPX plus VAX reduced the motor function of the GI tract in rats, and the reduced gut motility is likely mediated, at least in part, by inhibition of the excitatory neurotransmitter system.

Keywords: Gastric emptying; Rat; Small bowel transit; Subdiaphragmatic vagotomy; Unilateral thyroparathyroidectomy.

Figure 1

Schematic diagram of experiments to examine gastrointestinal motility after sequential application of unilateral thyroparathyroidectomy and subdiaphragmatic vagotomy. TPX: Thyroparatyroidectomy; VAX: Subdiaphragmatic vagotomy.

Figure 2

Effects of unilateral thyroparatyroidectomy plus subdiaphragmatic vagotomy on body weight gain in rats. Body weights were measured for 7 d from the day after subdiaphragmatic vagotomy (VAX). Each point represents the mean ± SE of 7-9 rats. ^bP < 0.01 vs normal and sham-operated groups. TPX: Thyroparatyroidectomy.

Figure 3

Changes in daily dietary intake in the thyroparatyroidectomy plus subdiaphragmatic vagotomy rats. Daily dietary intake (A: Absolute; B: Relative to body weight) was measured for 7 d from the day after subdiaphragmatic vagotomy (VAX). Each point represents the mean ± SE of 7-9 rats. ^aP < 0.05, ^bP < 0.01 vs normal and sham-operated groups. TPX: Thyroparatyroidectomy.

Figure 4

Effects of thyroparatyroidectomy plus subdiaphragmatic vagotomy on gastric emptying and small bowel transit in rats. Gastric emptying (A) and small bowel transit (B) was measured 8 d after subdiaphragmatic vagotomy (VAX). Each point represents the mean ± SE of 7-9 rats. ^bP < 0.01 vs normal and sham-operated groups. TPX: Thyroparatyroidectomy.

Figure 5

Effects of thyroparatyroidectomy plus subdiaphragmatic vagotomy on defecation of rats. Fecal pellet numbers (A) and weights (B) were measured for 7 d from the day after subdiaphragmatic vagotomy (VAX). Each point represents the mean ± SE of 7-9 rats. ^aP < 0.05, ^bP < 0.01 vs normal and sham-operated groups. TPX: Thyroparatyroidectomy.

Figure 6

Reduced contractile activity of the proximal colonic muscles in the thyroparatyroidectomy plus subdiaphragmatic vagotomy rats. Animals were sacrificed at 8 d after subdiaphragmatic vagotomy (VAX), and intact proximal colonic strips prepared from the age-matched normal and thyroparatyroidectomy (TPX) plus VAX rats were longitudinally or circularly mounted in a 10 mL organ bath. The contractile responses of colonic strips to acetylcholine (Ach) and N-nitro-L-arginine methyl ester (L-NAME) were measured by isometric force transducers. Figures show the representative tracings (A) and contractile responses to ACh (B) and L-NAME (C). Each point represents the mean ± SE of 7-9 rats. ^bP < 0.01 vs normal and sham-operated groups.

Figure 7

Reduced contractile activity of distal colonic muscles in the thyroparatyroidectomy plus subdiaphragmatic vagotomy rats. Animals were sacrificed at 8 d after subdiaphragmatic subdiaphragmatic vagotomy (VAX), and intact distal colonic strips prepared from the age-matched normal and thyroparatyroidectomy (TPX) plus VAX rats were longitudinally or circularly mounted in a 10 mL organ bath. The contractile responses of colonic strips to acetylcholine (Ach) and N-nitro-L-arginine methyl ester (L-NAME) were measured by isometric force transducers. Figures show the representative tracings (A) and contractile responses to ACh (B) and L-NAME (C). Each point represents the mean ± SE of 7-9 rats. ^aP < 0.05, ^bP < 0.01 vs normal and sham-operated groups.