Late hemodynamic changes following controlled hemorrhage and volume restitution with blood or Haemaccel in anesthetized portal hypertensive rats

BACKGROUND AND AIM: In portal hypertensive rats, hemorrhage and acute volume restitution with Haemaccel induced increased cardiac output and portal venous inflow. In the present study, the late hemodynamic effects of this procedure were explored. METHODS: Portal hypertension was induced by portal vein constriction. Blood was withdrawn 11.2 +/- 3.2 days later, at a rate of 0.3 mL/min, for 15 min, followed by 15 min of stabilization. Haemaccel or blood were infused at the same rate and volume used for withdrawal. Hemodynamic measurements were performed after 24 h, using radioactive microspheres. Viscosity was measured with an Ostwald viscometer. Vascular hindrance was calculated as resistance/viscosity ratio. RESULTS: Blood viscosity of the Haemaccel group (n = 11), was lower than in the blood group (n = 11): 2.7 +/- 0.2 versus 4.0 +/- 0.4 (P < 0.01). Arterial pressure, cardiac output, peripheral resistance, portal pressure, portal venous inflow and splanchnic arteriolar resistance were not significantly different. Splanchnic arteriolar and portocollateral hindrance were higher in the Haemaccel group (11.7 +/- 5.3 and 1.5 +/- 0.6 vs 7.7 +/- 3.0 and 0.9 +/- 0.4 mmHg x min x 100 gram body weight/mL, respectively, P < 0.05). CONCLUSION: In portal hypertensive rats, vital organs perfusion, 24 h after hemorrhage and isovolemic volume restitution with Haemaccel and blood, was similar. However, in Haemaccel-transfused animals, a reduction in vascular hindrance, indicating vasoconstriction, was observed in the splanchnic organs, which drain into the portal circulation. Vasoconstriction of the portocollateral vascular bed was observed as well. We suggest that slow-rate volume replacement during a portal-hypertensive-related bleeding episode enables hemodynamic adaptation to occur. Thus, undesirable hyperdynamic changes, which may aggravate secondary bleeding, are attenuated.     

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)     

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

ＥｆｅｃｔｓｏｆｔｅｔｒａｎｄｒｉｎｅｏｎｇａｓｔｒｉｃｍｕｃｏｓａａｎｄｌｉｖｅｒｉｎｐｏｒｔａｌｈｙｐｅｒｔｅｎｓｉｖｅｒａｔｓＭＵＹｉ，ＳＨＥＮＹａｏＺｏｎｇａｎｄＣＨＵＹｉＦａｎｇＳｕｂｊｅｃｔｈｅａｄｉｎｇｓｌｉｖｅｒｇａｓｔｒｉｃｍ...     

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.     

Nipradilol, a new β-blocker with vasodilatory properties, in experimental portal hypertension: A comparative haemodynamic study with propranolol

The haemodynamic effects of nipradilol, a new non-selective β-adrenoreceptor blocker with vasodilating actions like nitroglycerin, were examined in rats with portal hypertension due to portal vein stenosis. Portal hypertensive rats were divided into five groups receiving infusion of placebo, 3 mg of propranolol, 300, 600 and 1200 μg of nipradilol. At its highest dose, nipradilol achieved a reduction of 34.4 ± 4.4% in heart rate which was similar to that in the propranolol group (36.5 ± 2.4%). Also for other systemic haemodynamic parameters, the nipradilol 1200 μg group exhibited changes not significantly different from those in the propranolol group; mean arterial pressure (- 13 vs - 14%), cardiac index (- 37 vs - 31%) and systemic vascular resistance (+ 29 vs+ 32%). In contrast to the similar changes in the systemic circulation, a 1200 μg dose of nipradilol lowered portal pressure significantly more than propranolol (- 4.3 ± 0.6 vs - 2.9 ± 0.2 mmHg, P≤ 0.05). Nipradilol then reduced portal blood flow by 22% (P≤ 0.05) without a significant change in portocollateral resistance. On the other hand, propranolol not only caused a reduction in portal blood flow of 30% (P≤ 0.01), but also an increase in portocollateral resistance of 21% (P≤ 0.05). The results suggest that nipradilol may ensure a more effective control of portal hypertension than propranolol, presumably via its venodilatory action on portocollateral vessels.     

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 somatostatin on splanchnic hemodynamics in cirrhotic patients with portal hypertension

INTRODUCTION Esophageal variceal bleeding (EVB) is one of the most common complications of cirrhosis with portal hypertension. In recent years, great progress has been made in medicinal treatment. Somatostatin has been widely used in clinics, for it can effectively lower the portal venous pressure (PVP) with little side effect. The aim of this study is to assess the effect of somatostatin on portal venous pressue and splanchnic hemodynamics in patients with liver cirrhosis and portal hypertension.     

Acute effect of propranolol on splanchnic circulation in normal and portal hypertensive rats

Propranolol decreases portal venous pressure in patients with cirrhosis but no method is available in man to study the effect of this beta-blocker on splanchnic organ blood flow. Because in rats, the microsphere method allows evaluation of regional blood flow, the acute effect of propranolol on both splanchnic and systemic circulations was studied in normal rats and in rats with portal hypertension due to portal vein stenosis. Portal venous pressure significantly decreased during propranolol administration in normal (5.6 +/- 1.0-4.7 +/- 1.1 mm Hg; mean +/- SD) as well as in portal hypertensive rats (11.7 +/- 2.3-10.3 +/- 1.8 mm Hg). Propranolol slightly decreased cardiac output and arterial pressure in all rats. Portal tributary blood flow was significantly reduced by propranolol in normal rats (17.4 +/- 3.0-11.3 +/- 2.2 ml/min) and in portal hypertensive rats (23.7 +/- 5.0-16.6 +/- 3.3 ml/min). Accordingly vascular resistance of the different organs in the portal venous territory increased in these rats receiving propranolol. The percentage of the decrease in portal tributary blood flow was significantly more marked than the percentage of reduction in cardiac output in portal hypertensive rats but, in normal rats, these percentages were parallel. Hepatic arterial blood flow did not change or slightly increased and, consequently, hepatic arterial vascular resistance decreased. These findings further clarify the marked effects of propranolol on splanchnic circulation.     

Acute and 7-day portal pressure response to carvedilol and propranolol in cirrhotics

BACKGROUND: Carvedilol, a non-selective beta- and alpha-1 blocking agent, has portal hypotensive action. This study evaluates the acute and 7-day response to carvedilol, and compares it to that of propranolol. METHODS: Thirty-six cirrhotics were randomized into two groups of 18 each, and treated with carvedilol or propranolol. Hepatic venous pressure gradient (HVPG) was measured before and 90 min after either 25 mg carvedilol or 80 mg propranolol was administered orally, and again 7 days after 12.5 mg carvedilol daily or 80 mg propranolol daily, respectively. 'Responders' were defined as those with HVPG reduction of > or = 20%. RESULTS: With carvedilol, 11/18(61.1%) and 11/17(64.7%) patients responded acutely and after 7 days, respectively, while 9/18(50%) and 10/16(62.5%) did so to propranolol. However, HVPG reduction (percent) by carvedilol was not superior to that by propranolol either acutely (27.67 +/- 31.49 compared to 22.98 +/- 27.40, P = 0.6) or after 7 days (28.2 +/- 29.05 compared to 23.25 +/- 20.15, P = 0.6). With carvedilol, the acute HVPG response (P < 0.001) and responder status (P = 0.018) were good predictors of the response after 7 days, but were weak predictors in the case of propranolol (0.1 > P > 0.05 and P = 0.059, respectively). On carvedilol, only one patient (with ascites) developed symptomatic systemic hypotension with oliguria. CONCLUSION: Carvedilol is a relatively safe, effective portal hypotensive agent, both acutely and over 7 days, but not superior to propranolol, at least in Indians. The acute hemodynamic response seems promising in predicting long-term response.     

普萘洛尔联合5-单硝酸异山梨酯对肝硬化门静脉高压血流动力学参数的影响

目的探讨普萘洛尔联合5-单硝酸异山梨酯治疗对肝硬化门静脉高压患者血流动力学参数的影响。方法 30例肝功能Child-Pugh分级A、B级的肝硬化门静脉高压患者随机分为两组,其中普萘洛尔治疗组15例,普萘洛尔联合5-单硝酸异山梨酯治疗组15例,疗程均为48周。所有患者治疗前后均通过超声多普勒显像仪观察门静脉血流速度(VFP)和门静脉内径(PVD),并计算门静脉充血指数(PCI)。结果普萘洛尔组治疗前后VFP分别为(12.01±1.75)cm/s和(10.80±1.32)cm/s,PVD分别为(20.73±1.58)mm和(19.53±1.41)mm,差异均有统计学意义(P<0.05),PCI未显著下降(P>0.05);联合组治疗前VFP、PVD和PCI分别为(11.40±1.55)cm/s、(20.87±1.50)mm和(0.2940±0.4561),治疗后分别为(9.60±1.30)cm/s、(15.87±1.19)mm和(0.2107±0.4220),差异均有统计学意义(P均<0.05);两组比较治疗后的VFP、PVD和PCI差异均有统计学意义(P均<0.05)。结论普萘洛尔联合5-单硝酸异山梨酯较单用普萘洛尔能更有效地降低肝硬化门静脉高压血流动力学参数,具有预防上消化道出血的作用。     

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     

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.     

Effect of verapamil on splanchnic haemodynamics in a portal hypertensive rat model

To elucidate the effects of verapamil on splanchnic haemodynamics in rats with portal hypertension, verapamil was given at a low dose (0.2 mg/kg) and a high dose (2 mg/kg) to the rat model after portal vein ligation. Approximately 10% decrease in arterial pressure was caused by the low dose of verapamil, with significant decreases in cardiac output and portal venous inflow as well as reduced portal pressure; these were all indicative of a rise in portal vascular resistance. In contrast, the marked fall in both arterial pressure and cardiac output in the high dose, accompanied by a significant decrease in the portal pressure and the unchanged portal venous inflow, suggested a reduction in portal vascular resistance. This study shows that the acute effects of verapamil on portal hypertension may vary with the dosage used. These results also demonstrate that, since the therapeutic efficacy and safety of verapamil is only in a very limited range of dose, caution should be taken in its clinical use in the treatment of cirrhosis with portal hypertension.     

卡维地洛与普萘洛尔降低肝硬化门静脉高压患者肝静脉压力梯度效果的对比分析

目的探讨卡维地洛和普萘洛尔降低肝硬化门静脉高压患者肝静脉压力梯度(HVPG)的幅度、应答率以及用药后不良反应的差异,对卡维地洛降低门静脉压力的有效性和安全性进行评价。方法收集2010年10月-2012年1月在山东大学附属省立医院确诊的64名肝硬化门静脉高压患者,随机分为2组:普萘洛尔组(n=33)和卡维地洛组(n=31),根据血压和心率调整剂量,疗程7 d,均于治疗前后行HVPG测定及肝肾功能指标检测,比较2组患者HVPG降低的幅度及应答率,并观察患者低血压、腹水、肾损伤等不良反应的发生情况。计量资料组间比较采用t检验,计数资料组间比较采用χ2检验或Fisher精确概率法。结果卡维地洛组和普萘洛尔组的HVPG均明显降低,降低幅度分别为(28.30±22.19)%和(12.38±24.09)%,其中卡维地洛组降低更明显,差异有统计学意义(t=0.223 4,P=0.032)。2组应答率分别为:卡维地洛组56.7%(17/30),普萘洛尔组41.9%(13/31),2组差异无统计学意义(χ2=1.324,P=0.250)。卡维地洛组平均动脉压的降低较普萘洛尔组明显,差异有统计学意义(t=2.338,P=0.024),但患者未出现明显低血压的不良反应;2组患者胆红素、血肌酐和尿素氮在治疗前后无明显升高,亦无腹水生成或加重的趋势。结论本研究提示在短期内卡维地洛降低HVPG的作用较普萘洛尔显著,且无明显不良反应;其用于肝硬化门静脉高压的治疗是安全有效的。     

Effects of somatostatin analog on splanchnic hemodynamics and plasma glucagon level in portal hypertensive rats

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The effect of the combination of nitroglycerin and propranolol on splanchnic and systemic hemodynamics in a portal hypertensive rat model

Present investigations support major contributions from increases in both portal blood flow and portal vascular resistance in the mechanism that maintains portal hypertension. beta-Adrenergic blockers have been shown to reduce the elevated portal blood flow component. The possibility that nitroglycerin administration could reduce the elevated portal vascular resistance component is investigated here. Portal hypertension was induced in rats by a calibrated constriction of the portal vein. Portal hypertensive rats receiving placebo exhibited significant (p less than 0.05) elevations over normal rats receiving placebo in cardiac index, portal venous inflow and portal pressure. Portal hypertensive rats were then divided into groups receiving nitroglycerin infusion, propranolol (beta-adrenergic blockade) and combined administration of nitroglycerin and propranolol. Significant reductions (p less than 0.05) in portal blood flow of 30, 32 and 44%, respectively, were accompanied by significant portal pressure reductions of 2.7 +/- 0.2, 1.7 +/- 0.3 and 3.6 +/- 0.4 mm Hg in all groups, respectively (p less than 0.05). Nitroglycerin failed to prevent a 46% rise in portal-collateral resistance accompanying the portal blood flow reduction, similar to resistance rises also found in propranolol-treated (33%) and combination nitroglycerin-propranolol-treated (49%) groups. We conclude that nitroglycerin infusion can significantly reduce portal pressure, alone or in combination with beta-blockade, by reducing portal venous inflow. It appears that nitroglycerin reduces portal blood flow through the effect of baroreceptor sympathetic reflexes that constrict the splanchnic bed in response to vasodilatation and venous pooling.     

Expression of nitric oxide synthase protein and gene in the splanchnic organsof liver cirrhosis and portal hypertensive rats

AIM To investigate the expression of endothelial NO synthase (eNOS), inducible NO synthase (iNOS)protein and eNOS mRNA gene in the splanchnic organs of liver cirrhosis and portal hypertensive rats.METHODS In control and CCl4-induced liver cirrhotic rats, the expression of eNOS and iNOS proteins wasdetected by immunohistochemical method, and eNOS mRNA was detected by in situ hybridization.RESULTS The expression of eNOS protein and eNOS mRNA increased in most organs of the cirrhotic rats,including bronchial and alveolar epithelial cells, renal tubular epithelial cells and mesenchyma, endothelialand adventitial cells of aorta and superior mesenteric artery, whereas no significant increase of iNOS proteinwas found. In the hepatic tissue, NOS protein and eNOS mRNA were present in mesenchymal cells and vesseladventitial cells, no difference was observed in the expression between control and cirrhotic rats.CONCLUSION The expression of NOS varied in region. In splanchnic organs and vasculars there was anincreased expression of eNOS which induced aplanchnic vasodilation and increased the inflow of portal vein,while in the liver tissue and blood vessel showed no increased expression, which may be associated withincreased intrahepatic vascular resistance.     

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.     

缬沙坦、普萘洛尔对大鼠门脉高压性结肠病超微结构的影响

目的观察缬沙坦、普萘洛尔及两者联合应用对门脉高压性结肠病（PHC）大鼠结肠黏膜及黏膜下微循环的影响，并观察其超微结构的变化。方法采用复合因素法制备肝硬化门脉高压（PHT）大鼠模型，将大鼠分为模型组、治疗组（缬沙坦组、普萘洛尔组和联合用药组）、正常对照组。治疗组于第42天模型形成后分别予缬沙坦、普萘洛尔和两药联合灌胃，剂量分别为缬沙坦20mg／kg，每天1次；普萘洛尔22．5mg／kg，每天2次；联合组按前述方法同时给药；正常对照组与模型组给予等量自来水灌胃；连续15d。各组于治疗结束后测门静脉压力（PVP），取结肠组织，光镜下观察、测定黏膜下血管面积及血管扩张量化值，并进行透射电镜观察。结果与模型组比较，各治疗组均有明显降低PVP的作用，差异有统计学意义（P〈0．01），并以联合用药组PVP下降最明显。各治疗组结肠黏膜下微静脉面积及微静脉内径量化值均下降（P〈0．01），尤以联合用药组作用更为显著。各用药组结肠黏膜上皮吸收细胞微绒毛密集、排列较整齐，断裂少见，普萘洛尔组和联合用药组杯状细胞明显增多，腺上皮细胞线粒体较完整，缬沙坦和联合用药组分泌颗粒较多，尤以联合用药组显著。各治疗组毛细血管内皮细胞内吞饮小泡减少，未见明显肌微丝。结论缬沙坦和普萘洛尔均可减轻大鼠PHC结肠黏膜下血管扩张，改善结肠黏膜血供，对PHC大鼠的结肠黏膜有明显保护作用。