Systemic and splanchnic hemodynamics following hemorrhage and volume restitution with Haemaccel in portal hypertensive rats: The effect of propranolol

BACKGROUND AND AIMS: Recently, we found in a portal hypertensive rat model that hemorrhage and volume restitution with Haemaccel, a low viscosity plasma expander, induced an increase in cardiac output and portal venous inflow. The present study was conducted to evaluate whether pretreatment with propranolol will attenuate these hyperdynamic changes. METHODS: Portal hypertension was induced by portal vein constriction. Treatment was initiated 14--21 days later. Propranolol (30 mg/kg per day) or water were administered for 7 days via a gastric gavage. Under ketamine anesthesia, 18 h after the last given dose, blood was withdrawn at a constant rate of 0.3 mL/min for 15 min followed by a 15-min stabilization. Haemaccel was infused at the same rate and volume used for withdrawal. Hemodynamic measurements were performed after volume restitution in both groups by using radioactive microspheres. RESULTS: Eight rats were studied in each group. In the propranolol-treated animals, portal venous inflow was decreased (2.4 +/- 0.8 vs 3.8 +/- 0.7 mL/min per 100 g bodyweight; P < 0.01), while splanchnic arteriolar and porto-collateral resistance were increased (52.8 +/- 21.0 vs 32.8 +/- 13.0 and 6.0 +/- 1.4 vs 4.1 +/- 0.7 mmHg x min x 100 g bodyweight/mL; P < 0.05, respectively). Cardiac output, mean arterial pressure, heart rate, total peripheral resistance and portal pressure were not significantly different between the two groups. CONCLUSION: In this model, pretreatment with propranolol prevented the increase in portal venous inflow, which occurs following hemorrhage and volume restitution with Haemaccel. Although caution should be taken in extrapolating data from animal models to humans, our results suggest that volume replacement during a portal hypertensive-related bleeding episode may be safer in a patient treated with non-selective beta-adrenoreceptor antagonists.     

Acute hemodynamic changes following hemorrhage and volume restitution, using a low viscosity plasma expander, in anesthetized portal hypertensive rats

BACKGROUND/AIM: The aim of this study was to examine, in a portal hypertensive rat model, the hemodynamic changes following hemorrhage and volume restitution with blood and Haemaccel (a low viscosity, volume expander). METHODS: Portal hypertension was induced by portal vein constriction. Under ketamine anesthesia, blood was withdrawn at a constant rate of 0.3 ml/min, for 15 min followed by 15 min of stabilization. The shed blood or Haemaccel was infused at the same rate and volume used for withdrawal. Hemodynamic measurements were performed using radioactive microspheres. Blood viscosity was measured with an Ostwald viscometer. Vascular hindrance was calculated as the resistance/viscosity ratio. RESULTS: Twelve rats were studied in each group. During blood withdrawal, significant reductions in arterial pressure and portal pressure were observed. Volume replacement with blood was accompanied by increased mean arterial pressure and portal pressure to baseline. Arterial pressure following volume replacement with Haemaccel was lower and portal pressure was higher than baseline (128+/-16 and 17.1+/-3.9 vs 146+/-13 and 15.9+/-3.0 mmHg, respectively; p<0.05). Volume replacement with Haemaccel, compared to blood, was followed by increased cardiac output and portal venous inflow (39.3+/-11.6 and 4.4+/-1.5 vs 28.9+/-3 and 2.9+/-0.8 ml x min(-1) x 100 g bw(-1), respectively; p<0.05), decreased hematocrit and viscosity (29.3+/-3.8% and 2.8+/-1.3 vs 35.7+/-3.4% and 4.0+/-1.3, respectively; p<0.01) and decreased peripheral and splanchnic arteriolar resistance (3.6+/-1.4 and 29.2+/-14.0 vs 5.0+/-1.4 and 43.9+/-12.7 mmHg x ml(-1) x min x 100 g bw, respectively; p<0.05). There were no significant changes in vascular hindrance in any vascular beds between the two groups. CONCLUSION: In this model, volume replacement with Haemaccel induced an increase in cardiac output and portal venous inflow, thus preventing the reduction in portal pressure which might be expected when viscosity is reduced.     

Haemodynamic effects of chronic octreotide and tetrandrine administration in portal hypertensive rats

Octreotide is an effective portal hypotensive drug in the control of variceal bleeding. Tetrandrine is a type of calcium channel blocker recently reported to reduce portal hypertension. The present study was undertaken to investigate the haemodynamic effects of octreotide and tetrandrine, alone and in combination, in portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation. Portal hypertensive rats were allocated into one of the four groups: vehicle group (saline, 0.5 mL/day), octreotide group (100 μg/kg per 12 h), tetrandrine group (20 mg/kg per 12 h), and octreotide (100 μg/kg per 12 h) plus tetrandrine (20 mg/kg per 12 h) group. Tetrandrine or saline was administered by gavage, and octreotide by subcutaneous injection. The drug was given for 8 consecutive days, starting 1 day before ligation and continuing onwards. Haemodynamic parameters were measured thereafter, using the radioactive microsphere method. The portal venous pressure and portal tributary blood ?ow were signi?cantly reduced, while portal territory and renal vascular resistances were signi?cantly enhanced, by octreotide, tetrandrine, or octreotide plus tetrandrine in portal hypertensive rats, compared with the vehicle group. Our results showed that long-term administration of octreotide, tetrandrine, or octreotide plus tetrandrine led to portal hypotensive effects in portal hypertensive rats, but octreotide alone exerted better anti-hyperdynamic effects compared with tetrandrine alone. A combination of octreotide and tetrandrine offered no major bene?cial anti-hyperdynamic effects compared with octreotide alone.     

Haemodynamic effects of chronic tetrandrine treatment in portal hypertensive rats

Tetrandrine is a calcium channel antagonist with reported antihypertensive effect. However, the potential role of tetrandrine as a therapeutic agent in portal hypertension has yet to be explored. The present study aimed to investigate the haemodynamic effects of chronic tetrandrine treatment on portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation in Sprague-Dawley rats. Animals were allocated into one of two groups: a tetrandrine group and a vehicle group. Tetrandrine (20 mg/kg) or vehicle was administered by gavage every 12 h for 8 consecutive days, starting 1 day before ligation and continuing thereafter. After 8 days of tetrandrine treatment, systemic haemodynamics, organ blood flows and the degree of portal-systemic shunting were measured after an overnight fast. The portal venous pressure and portal tributary blood flow were significantly decreased, while portal territory as well as hepato-collateral vascular resistance significantly increased in the tetrandrine group compared with the vehicle group. The cardiac index was increased, while systemic vascular resistance was decreased, in the tetrandrine group. Mean arterial pressure, heart rate, portalsystemic shunting and bodyweight were similar between the two groups. Renal blood flow was decreased in the tetrandrine group. In conclusion, long-term treatment of tetrandrine reduced portal venous pressure and alleviated splanchnic hyperaemia in portal hypertensive rats without affecting the portal-systemic shunting.     

Effects of blood volume restitution following a portal hypertensive-related bleeding in anesthetized cirrhotic rats

The aim of this study was to investigate the influence of different strategies of blood volume restitution in the outcome of portal hypertension-related bleeding in anesthetized cirrhotic rats. Gastrointestinal hemorrhage was induced by sectioning a first order branch of the ileocolic vein in 38 cirrhotic rats (common bile duct ligation and occlusion). The subsequent hypovolemic shock was treated with no transfusion (n = 17), moderate transfusion (50% of expected blood loss, 5 mL, n = 11), and total transfusion (100% of expected blood loss, 10 mL, n = 10). At the end of the blood transfusion period (minute 15), mean arterial pressure (MAP) partially recovered in rats receiving moderate transfusion or no transfusion but decreased in the 10-mL transfusion group ( downward arrow 12 +/- 43%, P < .05 vs. no transfusion and 5 mL transfusion). After transfusion, groups given no or 5 mL transfusion remained hemodynamically stable. However, rats receiving 10 mL transfusion continued to deteriorate with persistent bleeding and progressive fall in MAP ( downward arrow 65 +/- 12%; P < .05 vs. no transfusion and 5 mL transfusion). Collected blood loss was significantly greater in the 10-mL group (20.0 +/- 1.5 g) than in groups given 5 mL (15.9 +/- 2.8 g; P < .05) or no transfusion (13.2 +/- 2.1 g; P < .05 vs. 10 mL and 5 mL transfusion). Survival in the no transfusion group was 47%. Rats given 5-mL transfusion had 64% survival. The worst survival was observed in the 10-mL transfusion group (0% survival; P < .05). We concluded that a transfusion policy aimed at completely replacing blood loss worsens the magnitude of bleeding and mortality from portal hypertensive-related bleeding in cirrhotic rats. On the contrary, moderate blood transfusion allowed hemodynamic stabilization and increased survival.     

Blood digestion-induced splanchnic hyperemia and portal blood flow in portal hypertensive rats and the role of octreotide

We aimed to investigate whether the presence of blood within the intestinal lumen after variceal bleeding would lead to reactive intestinal hyperemia, which in turn could result in the worsening of portal hemodynamics, and thus bleeding recurrence. Two models of portal hypertensive Wistar rats were used: 32 CCl₄-cirrhotics with a low index of portal-systemic shunting and 32 that had been previously subjected to portal vein stenosis, with a high index of portal-systemic shunting; 32 Wistar rats served as controls. The rats were divided into four groups, each comprising 8 cirrhotics, 8 portal vein stenosis rats, and 8 controls. Intestinal microcirculation and portal blood flow were assessed by laser-Doppler and transit-time ultrasonic flow probes, respectively, before and 60 min after the injection of 2 ml of blood (groups 1 and 2) or an equal volume of NaCl 0.9% (placebo; groups 3 and 4) into the intestinal lumen. Octreotide (0.2 μg/100 g body weight [BW]) (groups 1 and 3) or NaCl 0.9% (groups 2 and 4) was then given subcutaneously, and 30 min later the final measurements were performed. The presence of blood within the intestinal lumen resulted in an increase in intestinal microcirculation in rats in all groups, while portal blood flow was increased in portal vein stenosis rats and controls, and decreased in cirrhotics. The presence of NaCl 0.9% had no effect. Octreotide, but not NaCl 0.9%, led to a decrease in both intestinal microcirculation and portal blood flow. The findings of this study suggest that intestinal hyperemia induced by digestion of blood in the enteric lumen increases or decreases portal blood flow, the result being strongly related to the portal hypertension model used. Since the main difference between the models was the extent of portal-systemic shunting, this may suggest a relationship between portal blood flow and portal-systemic shunting. This relationship could explain why variceal bleeding stops in some patients but recurs in others. (Received Sept. 29, 1997; accepted Jan. 23, 1998)     

Short- and long-term hemodynamic response to octreotide in portal hypertensive patients: a double-blind,controlled study

Abstract: This randomized, double-blind, placebo-controlled study on the hemodynamic effect of two different doses of octreotide administered subcutaneously was conducted among 20 cirrhotic portal hypertensive patients. The wedged hepatic venous pressure, the hepatic venous pressure gradient, the mean portal venous flow velocity, the resistive index of the superior mesenteric artery, the heart rate and the mean arterial pressure were simultaneously evaluated by hepatic vein catheterization and Doppler flowmetry at baseline, 30 and 45 min after a subcutaneous injection of octreotide [0.10 mg (7 patients), 0.05 mg (7 patients)] and of a placebo (6 patients). The portal blood flow velocity, the resistive index of the superior mesenteric artery, the heart rate and the mean arterial pressure were also measured 2, 4, 6 and 8 h after the injection. The hemodynamic changes observed 30 min after the injection did not differ from those at 45 min and the changes at 2, 4, and 6 h were similar to those at 8 h. A statistically significant decrease, in comparison to the placebo group, was observed 45 min after the injection of the two doses of octreotide in the wedged hepatic venous pressure (cumulative median decrease: —10%, p<0.005), in the hepatic venous pressure gradient (cumulative median decrease: —10%, p<0.005) and in the mean portal flow velocity (cumulative median decrease: —11%, p<0.005). A significant increase in the resistive index of the superior mesenteric artery was observed 45 min after the injection of the two doses of octreotide (cumulative median increase: + 10%, p<0.005). Lower, but significant changes in the mean portal flow velocity and in the resistive index of the superior mesenteric artery persisted until 8 h after the injection of the two doses of octreotide (cumulative median decrease of mean portal flow velocity: —7%, p<0.005 and cumulative median increase of resistive index of the superior mesenteric artery: +4%, p<0.005). Changes in the wedged hepatic venous pressure, the hepatic venous pressure gradient, the mean portal flow velocity and the resistive index of the superior mesenteric artery showed a great variability among patients. These changes were more pronounced in patients injected with the lower dose with no relationship with the plasma drug concentrations. Responder patients showed a significant higher baseline mean portal flow velocity in comparison with nonresponders (15.2±1.7 cm/s vs 11.3 ±1.3 cm/s; p<0.005).     

Underlying mechanism of portal hypertensive gastropathy in cirrhosis: A hemodynamic and morphological approach

Background and Aim:  Portal hypertensive gastropathy (PHG) is an important cause of bleeding in patients with cirrhosis associated with portal hypertension. Histologically, the condition is characterized by dilation of the mucosal and submucosal vessels of the stomach; however, its mechanisms remain unclear. The aim of the present cross-sectional study was to evaluate the role of portal and systemic hemodynamic features, humoral factors and hepatocellular function in the development and severity of PHG in patients with cirrhosis.
Methods:  Forty-six patients with cirrhosis of different etiologies underwent endoscopy. Portal hypertension was evaluated by hepatic venous pressure gradient (HVPG). The gastric mucosa was analyzed using two diagnostic methods: endoscopy according to the McCormack criteria and histological by histomorphometric analysis.
Results:  The prevalence of PHG according to the endoscopic and histomorphometric methods was 93.4% and 76.1%, respectively. There were no statistically significant differences in HVPG measurements between the patients with mild (16.0 ± 5.9 mmHg) and severe PHG (16.9 ± 6.5 mmHg; P  = 0.80) or between patients who did not have (15.2 ± 8.0 mmHg) and those who had PHG (16.3 ± 5.7 mmHg). No correlation was found between the presence or severity of PHG and systemic vascular resistance index ( P  = 0.53 and 0.34, respectively), Child–Pugh classification ( P  = 0.73 and 0.78, respectively) or glucagon levels ( P  = 0.59 and 0.62, respectively).
Conclusions:  The present data show no correlation between the presence or the severity of PHG and portal pressure, Child–Pugh classification or systemic hemodynamics, suggesting that other factors may be involved in the physiopathology of PHG, such as local gastric mucosal factors or other underlying factors.     

门高压鼠血浆前列环素与门脉压力的关系

目的 探讨门脉压力升高和门体分流在前列环素（ＰＧＩ２）或高中的作用。方法 ３６只雄性ＳＤ大随机分为四组：肝前型（ＰＨＰＨ，ｎ＝８）和肝内型门高压（ＩＨＰＨ，ｎ＝９），端侧门腔分流（ＰＣＳ，ｎ＝８）以及手术对照组（ＳＯ，ｎ＝１１），模型制备后２周；（１）测游离门脉压（ＦＰＰ）；（２）应用核素微球技术研究全身及内脏血流血压学；（３）从股动脉采集血样用放射免疫法测血浆６－酮－前列腺素Ｆ１α（６－ｋｅｔｏ     

Hemodynamic effects of hypothyroidism induced by methimazole in normal and portal hypertensive rats

Portal hypertension is accompanied by a hyperdynamic circulatory state that shares some similarities with thyrotoxicosis. This study was conducted in order to investigate the hemodynamic effects of hypothyroidism in a rat model with portal hypertension induced by partial portal vein ligation (PVL). Four groups of 10 rats each were studied: normal control and hypothyroid rats, and PVL control and hypothyroid rats. Hypothyroidism was induced by methimazole 0.04% in drinking water. Hemodynamic measurements were performed using the radioactive microsphere technique. Induction of hypothyroidism was confirmed by elevated TSH levels. In the PVL groups, hypothyroidism ameliorated the hyperdynamic circulation. Portal venous inflow and portal pressure dropped significantly: 7.1±0.2 vs 4.8±0.3 ml/min/100 g body wt (P<0.01) and 13.4±0.9 vs 10.9±0.8 mm Hg; (P<0.01), respectively. In normal rats, hypothyroidism was manifested by a hypodynamic circulatory state. These results demonstrate that hypothyroidism induced by methimazole is followed by amelioration of the hyperdynamic circulation, normalization of portal venous inflow, and reduction of portal pressure.     

Effect of melatonin and misoprostol on bacterial translocation in portal hypertensive rats

Background and Aim: Portal hypertension is the main complication of cirrhosis and it is responsible for its most common complications. Bacterial translocation increases the morbidity and mortality rates in patients with portal hypertension. We aimed to investigate the effects of melatonin and misoprostol on bacterial translocation induced by portal hypertension. Methods: We established four groups, each containing eight rats. Except for the control and sham groups, the animals in the other groups (treatment groups) received misoprostol or melatonin for 3 days after the first operation. In the sham group, a laparotomy was carried out and only the portal vein was dissected. Calibrated portal vein ligation was carried out in the other groups. All animals were given 10¹⁰Escherichia coli by orogastric intubation 12 h before sampling. Seventy‐two hours after the first operation, mesenteric lymph node and blood samples were obtained and cultured. Two cc blood samples were obtained for a polymerase chain reaction study. A piece of terminal ileum was also sampled for histopathologic examination. Results: Mesenteric lymph node and blood cultures of all control animals were positive for microbiological growth, and polymerase chain reaction results were positive in seven of the eight rats. Histopathologically, edema, vasodilatation and inflammatory cell infiltration were found to be less in the other groups in comparison to the control group. The incidence of bacterial translocation was decreased in all treatment groups as compared to the control group. Conclusions: In this study, bacterial translocation occurred in portal hypertension. Melatonin and misoprostol reduced the incidence of bacterial translocation in portal hypertensive rats.     

Measurement of liver volume and its clinical significance in cirrhotic portal hypertensive patients

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Effects of tetrandrine on gastric mucosa and liver in portal hypertensive rats

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Structural and functional changes of the gastric mucosa in rats with portal hypertension

Structural and functional changes of the gastric mucosa were studied in rats made portal hypertensive by partially ligating the portal vein. Studies were carried out at either 3 or 12 days after ligation or sham operation. At 3 days, structural changes were greater than at 12 days, the major effects being vascular congestion in the lamina propria, muscularis mucosa, submucosa, and submucosal oedema. Transmission electron microscopy showed only a mild hyperplasia in the muscularis mucosa. Gastric blood flow appeared to decrease at 3 days post-ligation compared to sham-operated control rats, but was significantly increased by 12 days after ligation (P less than 0.01). Cardiac output also appeared to increase in the portal hypertensive rats by 12 days post-ligation but this was not statistically significant. Portal venous inflow was significantly increased by 12 days (P less than 0.05) but after correction for collateral circulation liver blood flow had returned to normal values by 12 days post-ligation.     

Role of endotoxaemia in hyperdynamic circulation in rats with extrahepatic or intrahepatic portal hypertension

This study investigated the role of endotoxaemia in the development of hyperdynamic circulation observed in rats with extrahepatic (high collateralization) or intrahepatic (low collateralization) portal hypertension. Compared with sham-operated rats, decreased mean arterial pressure and systemic vascular resistance were detected on days 1, 4 and 14 following partial portal vein ligation. By day 1, the cardiac index of portal vein-ligated rats was similar to that of sham-operated rats and progressively increased, thereafter, reaching statistically higher values on days 4 and 14. No differences in plasma endotoxin levels were found between portal vein-ligated and sham-operated rats throughout the observation period. Both carbon tetrachloride-induced cirrhotic rats with and without ascites had a higher cardiac index and lower systemic vascular resistance than those of control rats, and cirrhotic rats with ascites had the lowest systemic vascular resistance. Plasma endotoxin levels were higher in cirrhotic rats with ascites (8.6±2.0 pg/mL; P < 0.01) than those of control rats (2.2±0.3 pg/mL) and cirrhotic rats without ascites (2.4±0.6 pg/mL). These results suggest that factors other than endotoxaemia play a role in the development of hyperdynamic circulation observed in rats with extrahepatic portal hypertension and cirrhotic rats without ascites, but that endotoxaemia may contribute to the maintenance of hyperdynamic circulation found in cirrhotic rats with ascites. The severity of liver disease may be a more important factor than the presence of portosystemic shunting for the development of endotoxaemia in portal hypertensive states.     

Portal hypertensive effects of combined terlipressin and DL-028, a synthetic α1 adrenoceptor antagonist administration on anesthetized portal hypertensive rats

Abstract: Aims/Background: The purpose of this study was to investigate the therapeutic effects of terlipressin, alone or in combination with DL-028, a synthetic α₁-adrenoceptor antagonist on anesthetized portal hypertensive rats. Methods: Portal hypertension was induced by either partial portal vein ligation (PVL) or bile duct ligation (BDL) in Sprague-Dawley rats. Each portal hypertensive rat received only one of the two regimens: vehicle plus terlipressin or DL-028 plus terlipressin. Terlipressin dosage was 0.017 mg/kg/min infused for 3 min, while vehicle or DL-028 (0.50 μg/kg/min) was continuously infused for 40 min, starting 10 min before terlipressin infusion. Results: In PVL rats, infusions of vehicle plus terlipressin induced significant, maximum reduction of portal venous pressure (PVP, – 11.0±1.8%) and prominent elevation of mean arterial pressure (MAP, 50.3±9.0%) from baseline. Infusions of DL-028 plus terlipressin induced maximum PVP reduction (–17.5±2.8%) and MAP elevation (39.8±7.4%). In BDL rats, infusions of vehicle plus terlipressin also induced significant, maximum reduction of PVP (–6.8±2.1%) and prominent elevation of MAP (61.4±7.8%) from baseline. Infusions of DL-028 plus terlipressin induced maximum PVP reduction (–17.9±2.2%) and MAP elevation (47.9±7.4%). Compared to vehicle plus terlipressin, DL-028 significantly enhanced portal hypotensive effects of and attenuated systemic pressor effects of terlipressin in both PVL and BDL rats. Conclusions: Our results suggest that terlipressin, alone or in combination with DL-028, induced portal hypotensive effects in portal hypertensive rats. The combination of terlipressin with DL-028 was beneficial in enhancing the portal hypotensive effects and ameliorating the systemic pressor effects of terlipressin.     

Effects of calcium antagonists on hepatic and systemic hemodynamics in awake portal hypertensive rats

The effects of the calcium antagonists diltiazem and nicardipine on portal pressure and splanchnic blood flow were studied in awake, unrestrained portal hypertensive rats. Portal hypertension was induced in rats by partial portal vein ligation. Hemodynamic measurements were done using the radiolabeled microsphere technique. In portal veinligated and sham-operated rats, intraarterial diltiazem and nicardipine reduced mean arterial pressure. No significant changes, however, were observed in portal pressure and cardiac index. In portal vein-ligated rats, diltiazem and nicardipine increased portal tributary blood flow. Portal tributary vascular resistance was also significantly decreased. The decrease in the hepatocollateral vascular resistance prevented an increase in portal pressure. In sham-operated rats, these changes were not observed. It is possible that the vascular responses to calcium antagonists are altered in portal vein-ligated rats. These findings demonstrate that the hemodynamic effects of calcium antagonists occur at two levels. First, the increase in portal tributary blood flow appears to be a selective effect on portal tributary vascular resistance. Secondly, the portal pressure does not increase in parallel with the increase in portal tributary blood flow because of a similar reduction in portocollateral vascular resistance.     

Rapamycin prevents mesenteric neo‐angiogenesis and reduces splanchnic blood flow in portal hypertensive mice

Aim: Increased angiogenesis in the mesenteric microvasculature of portal hypertensive animals may contribute to the development of splanchnic vasodilation associated with portal hypertension (PHT). Experimental data suggest that rapamycin may reduce angiogenesis and tumour growth by inhibiting the vascular endothelial growth factor (VEGF) pathway. This study determines whether rapamycin can prevent the neoangiogenesis in the mesentery of portal hypertensive mice and may influence the splanchnic vasodilation. Methods: PHT was induced by partial portal vein ligation (PPVL). PPVL and Sham mice were treated daily with rapamycin or placebo for 2 weeks. Protein expressions of VEGF, CD 31, Akt and p70S6 kinase (mTOR signalling pathway) were evaluated. Mesenteric blood flow (MBF) was measured by a perivascular flow probe. Results: Increased mesenteric angiogenesis and VEGF protein levels were observed in PPVL_placebo mice compared to Sham_placebo mice. Rapamycin treatment caused significant reduction in CD 31 positive endothelial cells and VEGF protein in the PPVL_rapamycine group compared to the PPVL_placebo group, to levels comparable with Sham_placebo and Sham_rapamycine groups. MBF was significantly higher in PPVL_placebo mice compared to the Sham_placebo mice. Rapamycin decreased significantly the MBF in PPVL_rapamycine mice compared to PPVL_placebo mice. Phospo‐Akt and p70S6 kinase protein levels were increased in the mesenteric tissue of PPVL_placebo mice compared to Sham_placebo mice, which were also prevented by treatment with rapamycin. Conclusions: An increased VEGF dependent neo‐angiogenesis is present in the mesentery of portal hypertensive mice. Rapamycin prevents angiogenesis in the mesenteric tissue and decreases the mesenteric blood flow in portal hypertensive mice, at least in part through an anti‐VEGF activity and influence on the mTOR signalling pathway.