P2X7 receptor antagonist improves gastrointestinal disorders in spontaneously hypertensive rats

The purinergic system participates in the control of blood pressure. Hypertension promotes the occurrence of gastrointestinal disorders such as intestinal inflammation and gastric emptying delay. This study aimed i) to investigate the participation of the P2X7 receptor blocker Brilliant Blue G (BBG) on gastric emptying of solids and changes in oxidative stress in the gastric fundus, duodenum, and colon of spontaneously hypertensive rats (SHR) and ii) to study the putative relationship of this effect with the renin-angiotensin system. Rats were divided into five groups: Control, SHR, SHR+BBG, SHR+BBG+ATP, and SHR+BBG+ANG II. In the gastrointestinal tract, we assessed gastric emptying (GE) and oxidative stress markers (NOx, MPO, GSH, SOD). We observed a decrease in the GE rate (P<0.05) in SHR vs control rats (21.8±2.0% vs 42.8±3.5%). The decrease in GE was returned (P<0.05) to control levels by BBG in SHR rats (21.8±2.0% vs 41.6±3.2%). Co-administration of ATP or ANG II together with BBG bypassed the effect of the P2X7 antagonist on GE in SHR (P<0.05) (21.9±5.0% vs 25.6±3.0% vs 41.6±3.2%). The MPO activity increased (P<0.05) in the gastric fundus of SHR compared to control rats (6.12±2.26 vs 0.077±0.02 UMPO/mg tissue); this effect was prevented (P<0.05) by BBG (0.55±0.15 vs 6.12±2.26 UMPO/mg tissue). Data demonstrated that blockage of P2X7 receptors with BBG can improve the GE delay and oxidative stress biomarkers in SHR animals. This preventive effect of BBG on GE delay was abrogated by ANG II and ATP, thus prompting crosstalk between renin-angiotensin and the purinergic signaling systems underlying this phenomenon.

Acute extracellular fluid volume changes increase ileocolonic resistancce to saline flow in anesthetized dogs

We determined the effect of acute extracellular fluid volume changes on saline flow through 4 gut segments (ileocolonic, ileal, ileocolonic sphincter and proximal colon), perfused at constant pressure in anesthetized dogs. Two different experimental protocols were used: hypervolemia (iv saline infusion, 0.9 per cent NaCl, 20 ml/min, volume up to 5 per cent body weight) and controlled hemorrhage (up to a 50 per cent drop in mean arterial pressure). Mean ileocolonic flow (N = 6) was gradually and significantly decreased during the expansion (17.1 per cent P<0.05) and expanded (44.9 per cent, P<0.05) periods while mean ileal flow (N = 7) was significantly decreased only during the expanded period (38 per cent, P<0.05). Mean colonic flow (N = 7) was decreased during expansion (12 per cent, P<0.05) but returned to control levels during the expanded period. Mean ileocolonic sphincter flow (N = 6) was not significantly modified. Mean ielocolonic flow (n = 10) was also decreased after hemorhage (retracted period) by 17 per cent (P<0.05), but saline flow was not modified in the other separate circuitis (N = 6,5 and 4 for ileal, ileocolonic sphincter and colonic groups, respectively). The expansion effect was blocked by atropine (0.5 mg/kg, iv) both on the ileocolonic (N = 6) and ileal (N = 5) circuits. Acute extracellular fluid volume retraction and expansion increased the lower gastrointestinal resistances to saline flow. These effects, which could physiologically decrease the liquid volume being supplied to the colon, are possible mechanisms activated to acutely balance liquid volume deficit and excess.

Effects of acute volemic changes on jejunal compliance in dogs

1. Jejunal compliance (deltaV/deltaP) was calculated from the intraluminal pressures measured in anesthetized dogs in an in situ upper jejunal pouch (40-50-ml capcity) with intraluminal volumes of 10, 20, 30, 40 and 50 ml of fisotonic saline. 2. Measurements were made in the same animal during and after acute sequential alterations of the extracellular fluid (ECF) volume obtained by: a) acute intravenous (iv) infusion of isotonic saline, b) acute hemorrhage, and c) reinfusion of isotonic saline. 3. Expansion of the ECF volume caused a significant, reversible downward shift of the compliance curve, i.e., the jejunal pouch became less receptive to liquid distension. After saline infusion was discontinued, complicance gradually returned to control levels. 4. Acute loss a substantial volume of blood after ECF expansion gradually shifted the complicance curve upwards to levels significantly diferent from control, indicating that retraction of the ECF volume made the jejunal pouch more receptive to liquid distension. 5. Reinfusion of bled animals with saline rather than autologous blood also induced a significant decrease in jejunal complicance to below control levels. 6. The jejunal pouch as a suitable preparation for monitoring in vivo modifications of compliance induced by acute changes in ECF volume, especially when it was nearly "half-full" (i.e., filled with 20 ml), suggesting a critical relationship between the volume capacity of the pouch and its fluid content. 7. These results suggest that the modulation of the jejunal portion os small intestine compliance is involved in the processes that balance the ECF volume during acute life-threatening situations such as accidental hyperhydration or hemorrhage

Acute changes in extracellular fluid volume modify the antroduodenal flow of saline in dogs: a possible physiological role

The antroduodenal (AD) flow of saline was measured in anesthetized dogs following two different protocols of acute changes in extracellular fluid (ECF) volume, ECF expansion by in infusion of saline before or after hemorrhage decreased the AD flow; conversely, hemorrhage before or after expansion increased flow. These alternating modifications in the AD flow are independent of the sequence of volemic changes and may constitue part of the homeostatic responses of the gut to confront life-thratening situations such as accidental hyperhydration or hemorrhage