Spinal cord transection modifies ileal fluid and electrolyte transport in rats.

Spinal cord injury (SCI) is associated with severe autonomic changes, including inhibition of gastrointestinal (GI) motility. GI motility changes are known to affect electrolytes transport and these changes have not been adequately studied after SCI. We studied the ileal permeability to fluid and electrolytes in rats submitted to experimental spinal cord transection (SCT), between T4 and T5, throughout the first week after SCT. SCT increased ileal secretion of Na+ (P<0.05) and decreased the Cl(-) absorption during the first week post SCI (P<0.05). Water transport was also significantly altered, leading to increased water secretion following the Na+ gradient. Ileal secretion of K+ was significantly increased 1 and 7 days after spinal cord injury. To our knowledge, the present findings are the first direct evidence that SCT alters ileal electrolyte transport in rats. Further studies are necessary to evaluate the mechanisms involved in this phenomenon.

Subtotal nephrectomy inhibits the gastric emptying of liquid in awake rats.

Homeostasis of blood volume (BV) is attained through a functional interaction between the cardiovascular and renal systems. The gastrointestinal tract also adjusts its permeability and motor behavior after acute BV imbalances. We evaluated the effect of progressive nephron loss on gut motility. Male Wistar rats were subjected or not (sham) to 5/6 partial nephrectomy (PNX) in two steps (0 and 7th day). After further 3, 7, or 14 days, PNX and sham operation (control) rats were instrumented to monitor mean arterial pressure (MAP), central venous pressure (CVP), heart rate (HR), and blood collection for biochemical analysis. The next day, they were gavage fed with a liquid test meal (phenol red in glucose solution), and fractional dye recovery determined 10, 20, or 30 min later. The effect of nonhypotensive hypovolemia and the role of neuroautonomic pathways on PNX-induced gastric emptying (GE) delay were also evaluated. Compared with the sham-operated group, PNX rats exhibited higher (P < 0.05) MAP and CVP values as well as increased values of gastric dye recovery, phenomenon proportional to the BV values. Gastric retention was prevented by prior hypovolemia, bilateral subdiaphragmatic vagotomy, coelic ganglionectomy + splanchnicectomy, guanethidine, or atropine pretreatment. PNX also inhibited (P < 0.05) the marker's progression through the small intestine. In anesthetized rats, PNX increased (P < 0.05) gastric volume, measured by a balloon catheter in a barostat system. In conclusion, the progressive loss of kidney function delayed the GE rate, which may contribute to gut dysmotility complaints associated with severe renal failure.

Inhibitory effect of sildenafil on rat duodenal contractility in vitro: putative cGMP involvement.

1. Sildenafil citrate (Viagratrade mark; Pfizer, Sandwich, Kent, UK), a phosphodiesterase 5 inhibitor, rises cGMP levels in smooth muscle cells. It relaxes both vascular and visceral smooth muscle. In order to assess the intestinal effects of sildenafil, we decided to investigate its actions on rat duodenal motor activity in vitro. 2. In isolated duodenal segments maintained in Tyrode's solution, sildenafil exhibited a concentration-dependent antispasmodic effect on acetylcholine (ACh)-induced phasic contractions, with an IC50 value of 26.7 micromol/L (95% confidence interval (CI) 2.0-55.3 micromol/L). 3. Sildenafil also relaxed the carbamylcholine (CCh)-induced sustained contraction with an IC(50) of 16.2 micromol/L (95% CI 9.5-27.6 micromol/L). Sildenafil produced significant additional relaxation of 25.2 +/- 8.1% of the CCh-induced contraction, beyond basal tone. 4. Sildenafil reduced the amplitude of spontaneous duodenal contractions with an EC50 of 9.6 micromol/L (95% CI 5.7-16.2 micromol/L). This effect was significantly more potent than the effects of zaprinast and papaverine, which also reduced duodenal contractions with EC50 values of 91.6 micromol/L (95% CI 46.0-182.2 micromol/L) and 78.5 micromol/L (95% CI 37.1-166.3 micromol/L), respectively. 5. In preparations treated previously with methylene blue (10 micromol/L) or 1H-[1,2,4]oxadiazolo(4,3-a)quinoxalin-1-one (ODQ; 10 micromol/L), the EC50 values for the sildenafil effect were significantly increased to 39.0 micromol/L (95% CI 23.9-63.4 micromol/L) and 43.8 micromol/L (95% CI 24.5-78.3 micromol/L), respectively. These values were significantly greater than those obtained with sildenafil alone. 6. In conclusion, sildenafil has myorelaxant and antispasmodic effects on rat duodenal segments in vitro. The contractile inhibitory effect of sildenafil on rat isolated duodenum is probably due to intracellular cGMP accumulation as a result of its decreased degradation.

Sildenafil, a phosphodiesterase-5 inhibitor, delays gastric emptying and gastrointestinal transit of liquid in awake rats.

We studied the effect of sildenafil on gastric emptying (GE) and gastrointestinal (GI) transit in awake rats. After cervical vessel cannulation and 24 hr of fasting, the animals received an intravenous (IV) injection of sildenafil (4 mg/kg) or vehicle. Next they were gavage fed (1.5 ml) with a test meal (phenol red in 5% glucose solution, 0.5 mg/ml) and sacrificed 10, 20, or 30 min later. Experimental and control subsets consisted of 5-10 rats. Gastric and proximal, medial, and distal small intestine dye retentions (GDR and IDR, respectively) were obtained by spectrophotometry. Data were compared by ANOVA and Student-Newman-Keuls test. In sildenafil-treated animals, GDR increased (P < 0.05) by 20.3%, 46.9%, and 55,5% while medial IDR decreased (P < 0.05) by 35.1%, 43.4%, and 41.6%, respectively, at 10, 20, and 30-min intervals. Proximal and distal IDR values did not change in sildenafil-treated animals. Mean arterial pressure (MAP) decreased 25% (P < 0.05) right after sildenafil administration but normalized afterwards while in controls MAP remained unchanged. In conclusion, sildenafil delays GE and GI transit of a liquid meal while transiently decreases MAP in awake rats.

Gastric emptying and gastrointestinal transit of liquid in awake rats is delayed after acute myocardial infarction.

The outcome of acute myocardial infarction (AMI) on gastrointestinal motor behavior was assessed in awake rats. Under anesthesia, they were submitted to thoracotomy followed or not by occlusion of the left coronary artery. Next day, they were gavage fed (1.5 ml) with phenol red in 5% glucose solution and sacrificed 10, 20, or 30 min later. Each subset consisted of 7 to 19 animals. Dye recovery in the stomach, proximal, mid, and distal small intestine was obtained by spectrophotometry. Infarcted left ventricle plus septum area was about 48.9 +/- 2.8, 55.1 +/- 6.7, and 54.1 +/- 8.1% (respectively, for 10-, 20-, and 30-min subsets). AMI increased gastric dye retention by 25.5, 51.3, and 65.1% (respectively, for 10-, 20-, and 30-min subsets), while it decreased mid small intestine retention at 30 min (45.3%) as well as distal retention at 10 min (90.5%) and 20 min (90%). A positive correlation (rS = 0.64) was found between infarcted area and gastric retention values at 10 min. AMI also increased (P < 0.05) central venous pressure values in all subsets (3.8 +/- 0.2 vs. -2.1 +/- 1.5, 1.4 +/- 0.1 vs. 0.5 +/- 0.2, and 1.6 +/- 0.4 vs. -0.2 +/- 0.3 cm H2O), while it decreased (P < 0.05) mean arterial pressure (95.0 +/- 2.6 vs. 110.0 +/- 3.9 and 106.0 +/- 2.0 vs. 113.0 +/- 3.0 mm Hg, respectively, at 10 and 30 min), and increased (P < 0.05) the 10-min heart rate values (429.6 +/- 11.3 vs. 374.0 +/- 19.8 bpm). Omeprazole pretreatment did not alter this phenomenon. In another group of rats, cardiac chemoreflex stimulation by i.v. phenylbiguanide increased gastric dye retention by 51.1%. In conclusion, AMI delays the gastric emptying and gastrointestinal transit of liquid in awake rats.