Chronic Administration of Octreotide Increases Vascular Responsiveness in Rats with Portal Hypertension

1996 ◽  
Vol 91 (5) ◽  
pp. 601-606 ◽  
Author(s):  
Yi-Tsau Huang ◽  
Ju-Fen Tsai ◽  
Tsun-Bin Liu ◽  
Chuang-Ye Hong ◽  
May C.-M. Yang ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Portal Vein ◽  
Mesenteric Artery ◽  
Portal Pressure ◽  
Chronic Administration ◽  
Treated Group ◽  
Contractile Responses ◽  
Vascular Responsiveness ◽  
Octreotide Treatment ◽  
Vehicle Treated Group

1. It has been reported that octreotide partially corrects the hyperdynamic state in patients and animals with portal hypertension. The aim of the present study was to investigate whether chronic administration of octreotide can increase vascular responsiveness in rats with portal hypertension. 2. Portal hypertension was induced by partial portal vein ligation. Octreotide was given for 9 days subcutaneously (100 μg/kg every 12 h) starting 1 day before ligation. The aorta and mesenteric artery were then removed to study contraction after pressure recording. 3. Octreotide treatment significantly reduced portal pressure and plasma glucagon concentrations compared with the vehicle-treated group. Both phenylephrine and vasopressin induced concentration-dependent contractile responses in the aorta and mesenteric artery from both groups. The maximum contractile responses to phenylephrine and vasopressin in aorta and mesenteric artery were significantly greater in the octreotide-treated group than in the vehicle-treated group. The EC50 values for phenylephrine and vasopressin were significantly different in the aorta, but not in the mesenteric artery, between the two groups. In contrast, octreotide treatment did not alter the contractile responsiveness of arteries from sham-operated rats. 4. These results show that, in rats with portal vein stenosis, octreotide increases arterial contractile responsiveness and reduces portal pressure.

Chronic Administration of Octreotide Ameliorates Portal Hypertension and Portal Hypertensive Gastropathy in Rats with Cirrhosis

1998 ◽  
Vol 94 (4) ◽  
pp. 367-371 ◽  
Author(s):  
Che-Chang Chan ◽  
Fa-Yauh Lee ◽  
Sun-Sang Wang ◽  
Full-Young Chang ◽  
Han-Chieh Lin ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Carbon Tetrachloride ◽  
Portal Pressure ◽  
Chronic Administration ◽  
Portal Hypertensive Gastropathy ◽  
Cross Sectional ◽  
Hyperdynamic Circulation ◽  
Morphometric Analyses ◽  
Octreotide Treatment ◽  
To Receive

1. Portal hypertension and hyperdynamic circulation have been postulated to play a role in the pathogenesis of portal hypertensive gastropathy. Administration of octreotide to portal hypertensive rats has been shown to reduce portal pressure and ameliorate hyperdynamic circulation. 2. This study investigated the effects of chronic administration of octreotide on systemic and portal haemodynamics and the development of portal hypertensive gastropathy in carbon tetrachloride-induced cirrhotic rats. 3. After 12 weeks of carbon tetrachloride induction, cirrhotic rats were randomly assigned to receive either placebo (5% dextrose in water) or octreotide (65 μg/kg in 5% dextrose in water) subcutaneously twice daily for 10 days. Haemodynamic studies with a thermodilution technique and gastric morphometric analyses were performed at 10 days after treatment. 4. In cirrhotic rats, octreotide treatment induced a significant increase in systemic vascular resistance (2.7 ± 0.2 versus 3.4 ± 0.2 mmHg/ml · min−1 · 100 g−1, P < 0.05) and decrease in portal pressure (12.5 ± 1.2 versus 9.9 · 0.5 mmHg, P < 0.05) compared with placebo-treated rats. In addition, octreotide treatment significantly reduced the mean cross-sectional area of gastric mucosal vessels (2290 ± 145 versus 1810 ± 101 μm2, P < 0.05). 5. This study shows that chronic octreotide treatment ameliorates the development of portal hypertensive gastropathy in cirrhotic rats. The effect of octreotide on portal hypertensive gastropathy may, at least partly, be due to the alleviation of portal hypertension and hyperdynamic circulation.

Role of Haematocrit in Mediating the Actions of Chronic Erythropoietin Treatment on Blood Pressure and Renal Haemodynamics in the Rat

1993 ◽  
Vol 85 (6) ◽  
pp. 717-724 ◽  
Author(s):  
Chunlong Huang ◽  
Gerard Davis ◽  
Edward J. Johns
Keyword(s):  
Blood Pressure ◽  
Direct Action ◽  
Chronic Administration ◽  
Treated Group ◽  
Recombinant Erythropoietin ◽  
Doppler Flowmetry ◽  
Human Recombinant Erythropoietin ◽  
Vascular Responsiveness ◽  
Erythropoietin Treatment ◽  
Renal Vascular

1. This investigation aimed to study the effect of chronic administration of human recombinant erythropoietin on haematocrit, blood pressure, renal cortical and papillary resistances and vascular responsiveness to vasoconstrictor agents. 2. Rats were treated with placebo or 25, 50 or 100 units/kg erythropoietin subcutaneously, every other day for 3 weeks. Animals were then anaesthetized with sodium pentobarbitone and were prepared for laser-Doppler flowmetry measurement in the renal cortex and papilla. 3. Haematocrit in the placebo-treated group was 48.0 + 0.5% and was raised to 52.5 + 0.7, 55.9 + 0.8 and 62.4 + 1.1% (all P <0.05) by the chronic administration of 25, 50 and 100 units/kg doses of the hormone, respectively. Blood pressure was 107 + 1 mmHg in the placebo-treated group and was elevated to 116 + 2 and 130 + 1 mmHg (both P <0.05), respectively, by the two highest doses of erythropoietin. Cortical and papillary perfusions were reduced at the highest dose of erythropoietin, but calculated resistances were increased by 15 and 40% (P <0.05) at 50 and 100 units/kg doses of the hormone, respectively. 4. Infusion of the vasopressor hormones vasopressin and phenylephrine caused increases in blood pressure and decreases in renal cortical and papillary perfusion, the magnitudes of which were only marginally changed by the highest dose of the erythropoietin. Angiotensin II increased blood pressure and decreased cortical perfusion, and the magnitudes of these responses were unchanged by the chronic treatment with erythropoietin. 5. Acute graded increases in haematocrit resulted in significantly (P <0.05) raised blood pressure above a value of 58%. However, renal cortical and papillary perfusions decreased and resistances were increased significantly (P <0.05) when the haematocrit was raised above 56%. 6. The acute transfusion study demonstrated that elevations in blood pressure and renal vascular resistances occurred at haematocrit values somewhat higher than when it was raised by chronic erythropoietin treatment. Thus this would be consistent with the suggestion that erythropoietin has some direct action on the vasculature beyond that resulting from the raised haematocrit. These data show that a low dose regimen of erythropoietin can modestly increase haematocrit without other cardiovascular changes becoming apparent. The findings add weight to the recent clinical practice of using very low doses of the hormone in the treatment of chronic renal failure.

Electroacupuncture attenuates vascular hyporeactivity in a rat model of portal hypertension induced by bile duct ligation

2021 ◽  
pp. 096452842110392
Author(s):  
Yu-Sheng Chen ◽  
Chorng-Kai Wen ◽  
Geng-Hao Liu ◽  
Tzung-Yan Lee
Keyword(s):  
Portal Hypertension ◽  
Growth Factor ◽  
Bile Duct ◽  
Bile Duct Ligation ◽  
Portal Pressure ◽  
Contractile Responses ◽  
Hyperdynamic Circulation ◽  
Duct Ligation ◽  
Tnf Α ◽  
Cox 1

Background: A hyperdynamic circulation and impaired vascular responsiveness to vasoconstrictors are observed in portal hypertension (PHT) rats. Inflammation is a major contributor to the hyperdynamic circulation state in murine models of PHT. Electroacupuncture (EA) may ameliorate the inflammatory response and limit arterial vasodilatation and portal pressure. This study investigated the possible mechanisms underlying putative hemodynamics effects of EA in normal and PHT rats. Methods: PHT was induced by bile duct ligation (BDL) surgery over 4 weeks in rats. Sham-operated and BDL rats were treated with low-frequency EA (2 Hz) at ST36 10 min three times weekly for one or two consecutive weeks (for a total of 3 or 7 treatments, respectively). Serum tumor necrosis factor-α (TNF-α), nitrite/nitrate (NOx) and 6-keto-prostaglandin F1α (6-keto-PGF1α) were analyzed, and hemodynamic variation and contractile responses to phorbol-12,13-dibutyrate and phenylephrine in aortic and superior mesenteric arterial rings were recorded. Inducible (i) and endothelial (3) nitric oxide synthase (NOS), cyclooxygenase-1 (COX-1), and protein kinase C-α (PKC-α) levels were determined by Western blotting. Results: EA significantly reduced portal pressure and serum TNF-α, NOx and 6-keto-PGF1α levels compared to the untreated BDL group, enhanced maximum contractile responses in the aorta, up-regulated PKC-α, and down-regulated iNOS and COX-1 levels. In addition, EA decreased the aortic angiogenesis signaling cascade, reflected by down-regulation of vascular endothelial growth factor (VEGF) abundance and transforming growth factor β receptor (TGFβR)I/II expression, as assessed by immunostaining. Conclusion: EA attenuates TNF-α, NO and 6-keto-PGF1α overproduction, modulates the vascular levels of constitutive NOS and PKC-α, blunts the development of the angiogenesis cascade, and enhances vascular contractile force in PHT rats.

scholarly journals The Surgical Treatment for Portal Hypertension: A Systematic Review and Meta-Analysis

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Lanning Yin ◽  
Haipeng Liu ◽  
Youcheng Zhang ◽  
Wen Rong
Keyword(s):  
Portal Hypertension ◽  
Portal Vein ◽  
Variceal Bleeding ◽  
Meta Analysis ◽  
Portal Pressure ◽  
Combined Treatment ◽  
Cochrane Library ◽  
Quality Of Reporting ◽  
Portal Vein Pressure ◽  
Shunt Procedure

Aim. To compare the effectiveness of surgical procedures (selective or nonselective shunt, devascularization, and combined shunt and devascularization) in preventing recurrent variceal bleeding and other complications in patients with portal hypertension. Methods. A systematic literature search of the Medline and Cochrane Library databases was carried out, and a meta-analysis was conducted according to the guidelines of the Quality of Reporting Meta-Analyses (QUOROM) statement. Results. There were a significantly higher reduction in rebleeding, yet a significantly more common encephalopathy () in patients who underwent the shunt procedure compared with patients who had only a devascularization procedure. Further, there were no significant differences in rebleeding, late mortality, and encephalopathy between selective versus non-selective shunt. Next, the decrease of portal vein pressure, portal vein diameter, and free portal pressure in patients who underwent combined treatment with shunt and devascularization was more pronounced compared with patients who were treated with devascularization alone (). Conclusions. This meta-analysis shows clinical advantages of combined shunt and devascularization over devascularization in the prevention of recurrent variceal bleeding and other complications in patients with portal hypertension.

scholarly journals INVOLVEMENT OF CATECHOLAMINES IN THE MYOCARDIUM OF RATS SUBMITTED TO EXPERIMENTAL MODEL OF PORTAL HYPERTENSION

2018 ◽  
Vol 31 (3) ◽  
Author(s):  
Antonella VINHOLI ◽  
Marília Da Cruz FAGUNDES ◽  
Danieli Cristina PIGOZZO ◽  
Fernando Bermudez KUBRUSLY ◽  
Luiz Fernando KUBRUSLY ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Tyrosine Hydroxylase ◽  
Portal Vein ◽  
Mesenteric Artery ◽  
Wistar Rats ◽  
Statistical Significance ◽  
Immunohistochemical Analysis ◽  
Immunohistochemical Expression ◽  
Marked Area

ABSTRACT Background: The role of autonomic nervous system in the development and maintenance of portal hypertension is not fully elucidated. It is known that the gene expression of norepinephrine in the superior mesenteric artery varies with time, and it may contribute for splanchnic vasodilation and its consequent hemodynamic repercussions. It is still not known exactly how the adrenergic expression behaves at the heart level in the initial stages of this process. Aim: To evaluate the immunohistochemical expression of the enzyme tyrosine hydroxylase (tyrosine 3-monooxygenase), involved in the synthesis of norepinephrine, in the myocardium of rats submitted to partial ligation of the portal vein. Methods: Twenty-four Wistar rats were divided into two groups: Sham Operated and Portal Hypertension. The partial ligation was performed in the Portal Hypertension group, and after 1/6/24 h and 3/5/14 days the animals were euthanized. Immunohistochemical analysis was performed to quantify the expression of the stained enzyme using the ImageJ program. Results: The Portal Hypertension group expressed percentages between 4.6-6% of the marked area, while the Sham Operated group varied between 4-5%. Although there was no statistical significance, the percentage stained in the Portal Hypertension group followed an increasing pattern in the first 6 h and a decreasing pattern after 24 h, which was not observed in the Sham Operated group. Conclusion: The expression of noradrenaline in rat myocardium during the first two weeks after partial ligation of the portal vein, with tyrosine hydroxylase as marker, did not show differences between groups over time.

iNOS expression in vascular resident macrophages contributes to circulatory dysfunction of splanchnic vascular smooth muscle contractions in portal hypertensive rats

2011 ◽  
Vol 300 (3) ◽  
pp. H1021-H1031 ◽  
Author(s):  
Masahiro Kajita ◽  
Takahisa Murata ◽  
Kazuhide Horiguchi ◽  
Masateru Iizuka ◽  
Masatoshi Hori ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Portal Vein ◽  
Mesenteric Artery ◽  
No Synthase ◽  
Inos Expression ◽  
Inos Mrna ◽  
Hypertensive Rats ◽  
Vascular Walls ◽  
In Vitro Organ Culture

Portal hypertension, a major complication of cirrhosis, is caused by both increased portal blood flow due to arterial vasodilation and augmented intrahepatic vascular resistance due to sinusoidal constriction. In this study, we examined the possible involvement of resident macrophages in the tone regulation of splanchnic blood vessels using bile duct ligated (BDL) portal hypertensive rats and an in vitro organ culture method. In BDL cirrhosis, the number of ED2-positive resident macrophages increased by two- to fourfold in the vascular walls of the mesenteric artery and extrahepatic portal vein compared with those in sham-operated rats. Many ED1-positive monocytes were also recruited into this area. The expression of inducible nitric oxide (NO) synthase (iNOS) mRNA was increased in the vascular tissues isolated from BDL rats, and accordingly, nitrate/nitrite production was increased. Immunohistochemistry revealed that iNOS was largely expressed in ED1-positive and ED2-positive cells. We further analyzed the effect of iNOS expression on vascular smooth muscle contraction using an in vitro organ culture system. iNOS mRNA expression and nitrate production significantly increased in vascular tissues (without endothelium) incubated with 1 μg/ml lipopolysaccharide (LPS) for 6 h. Immunohistochemistry indicated that iNOS was largely expressed in ED2-positive resident macrophages. α-Adrenergic-stimulated contractility of the mesenteric artery was greatly suppressed by LPS treatment and was restored by NG-nitro-l-arginine methyl ester (NO synthase inhibitor); in contrast, portal vein contractility was largely unaffected by LPS. Sodium nitroprusside (NO donor) and 8-bromo-cGMP showed greater contractile inhibition in the mesenteric artery than in the portal vein with decreasing myosin light chain phosphorylation. In the presence of an α-adrenergic agonist, the mesenteric artery cytosolic Ca2+ level was greatly reduced by sodium nitroprusside; however, the portal vein Ca2+ level was largely unaffected. These results suggest that the induction of iNOS in monocytes/macrophages contributes to a hypercirculatory state in the cirrhosis model rat in which the imbalance of the responsiveness of visceral vascular walls to NO (mesenteric artery >> portal vein) may account for the increased portal venous flow in portal hypertension.

Systemic and splanchnic haemodynamic effects of pentifylline in rats with portal hypertension

1992 ◽  
Vol 83 (1) ◽  
pp. 41-45 ◽  
Author(s):  
M. Dagenais ◽  
G. Pomier-Layrargues ◽  
B. Rocheleau ◽  
L. Giroux ◽  
P.-M. Huet
Keyword(s):  
Cardiac Output ◽  
Portal Hypertension ◽  
Portal Vein ◽  
Portal Pressure ◽  
Reference Sample ◽  
Peripheral Resistance ◽  
Haemodynamic Effects ◽  
Portal Vein Ligation ◽  
Portal Venous Flow ◽  
Venous Flow

1. The systemic and splanchnic haemodynamic effects of pentifylline (40 mg/kg body weight intravenously) were assessed in rats with portal hypertension associated either with CCl4-induced cirrhosis (n= 13) or portal vein ligation (n=13). 2. Heparinized catheters were placed into the portal vein, inferior vena cava, aorta and left ventricle with exits from the neck. Haemodynamic studies were performed 4 h after consciousness was regained. Cardiac output and regional blood flows were measured using radiolabelled microspheres and the reference sample method in seven rats in each group; portal-systemic shunting was measured using microsphere injection in the ileo-colic vein in six rats in each group. 3. Forty-five minutes after injection, pentifylline had no effect on mean arterial pressure, cardiac output, peripheral resistance, portal venous flow, hepatic artery flow or portal-systemic shunting in either group of rats with portal hypertension. The drug lowered portal pressure (−18%) in cirrhotic rats, but not in portal-vein-ligated rats. 4. These data demonstrate that pentifylline lowers portal pressure in cirrhotic rats without affecting portal venous flow and portal-systemic shunting; this effect is possibly mediated by changes in intrahepatic resistance related to the effects of pentifylline on blood viscosity and/or on intrahepatic vasomotor tone.

Portal venous pressure and portasystemic shunting in experimental portal hypertension

1989 ◽  
Vol 257 (1) ◽  
pp. G52-G57 ◽  
Author(s):  
J. G. Geraghty ◽  
W. J. Angerson ◽  
D. C. Carter
Keyword(s):  
Portal Hypertension ◽  
Portal Vein ◽  
Venous Pressure ◽  
Portal Pressure ◽  
Rapid Change ◽  
Quadratic Function ◽  
Portal Venous Pressure ◽  
Portal Vein Ligation ◽  
Strong Positive Correlation ◽  
The Relationship

The relationship between portal venous pressure and the degree of portasystemic shunting was studied in portal vein-ligated and cirrhotic rats anesthetized with halothane. One day after partial portal vein ligation there was a strong positive correlation (r = 0.80, n = 7) between portal pressure and shunting of mesenteric venous blood as measured by injection of radioactive microspheres. The relationship subsequently underwent rapid change but stabilized by 14 days postligation, when higher levels of shunting were again associated with higher portal pressures up to a limit of approximately 70% shunting, above which pressures did not increase further. This relationship was well described by a quadratic function (r = 0.75, n = 17). In cirrhotic rats there was no relationship between portal pressure and shunting (r = -0.01, n = 10). The results suggest that in the prehepatic model there is little inherent variability in capacity to develop shunts, which open to a degree directly related to portal pressure, but that this relationship may be altered in cirrhotic portal hypertension.

Evolution of portal hypertension and mechanisms involved in its maintenance in a rat model

1985 ◽  
Vol 248 (6) ◽  
pp. G618-G625 ◽  
Author(s):  
E. Sikuler ◽  
D. Kravetz ◽  
R. J. Groszmann
Keyword(s):  
Blood Flow ◽  
Portal Hypertension ◽  
Portal Vein ◽  
Rat Model ◽  
Portal Pressure ◽  
Portal System ◽  
Hypertensive Rats ◽  
Hemodynamic Changes ◽  
Sequence Of Events ◽  
Radioactive Microsphere

In rats with portal hypertension induced by partial ligation of the portal vein, we have recently demonstrated an increased portal venous inflow that becomes an important factor in the maintenance of portal hypertension. The sequence of events that leads into this circulatory disarray is unknown. We evaluated chronologically the chain of hemodynamic changes that occurred after portal hypertension was induced by partial ligation of the portal vein. In this model it is possible to follow, from the initiation of the portal-hypertensive state, the interaction between blood flow and resistance in the portal system as well as the relation between the development of portal-systemic shunting and the elevated portal venous inflow. The study was performed in 45 portal-hypertensive rats and in 29 sham-operated rats. Blood flow and portal-systemic shunting were measured by radioactive microsphere techniques. The constriction of the portal vein was immediately followed by a resistance-induced portal hypertension characterized by increased portal resistance (9.78 +/- 0.89 vs. 4.18 +/- 0.71 dyn X s X cm-5 X 10(4), mean +/- SE, P less than 0.01), increased portal pressure (17.7 +/- 0.9 vs. 9.5 +/- 0.6 mmHg, P less than 0.001), and decreased portal venous inflow (3.93 +/- 0.26 vs. 6.82 +/- 0.49 ml X min-1 X 100 g body wt-1, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

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