Beneficial effects of combined terlipressin and tetramethylpyrazine administration on portal hypertensive rats

1999 ◽  
Vol 77 (8) ◽  
pp. 618-624 ◽  
Author(s):  
Fang-Chi Chang ◽  
Yi-Tsau Huang ◽  
Han-Chieh Lin ◽  
Chuang-Ye Hong ◽  
Jaung-Geng Lin ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Venous Pressure ◽  
Peripheral Resistance ◽  
Therapeutic Effects ◽  
Portal Vein Ligation ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Beneficial Effects ◽  
Sprague Dawley Rats ◽  
Duct Ligation

The purpose of this study was to investigate the therapeutic effects of terlipressin (TP) alone or in combination with tetramethylpyrazine (TMP) on anesthetized portal hypertensive rats. Portal hypertension was induced by either partial portal vein ligation (PVL, without cirrhosis) or bile duct ligation (BDL, with cirrhosis) in Sprague-Dawley rats. Each PVL or BDL rat received only one of the two regimens: vehicle for 3 min followed by TP (0.017 mg·kg-1·min-1 for 3 min) or TMP (10 mg·kg-1·min-1 for 3 min) followed by TP. In PVL rats, infusion of vehicle followed by TP induced significant reduction of portal venous pressure (PVP, -15.0 ± 1.0%) and prominent elevation of mean arterial pressure (MAP, 57.3 ± 8.1%) as well as total peripheral resistance (TPR, 113 ± 11%) from baseline, and there was a cardiodepressant response (cardiac index, CI, -26.3 ± 1.1%). Infusion of TMP followed by TP induced significant reduction of PVP (-20.3 ± 0.4%) and CI (-9.9 ± 1.2%) and significant elevation of MAP (31.3 ± 2.5%) and TPR (46.0 ± 4.1%) from baseline. In BDL rats, infusion of vehicle followed by TP also induced significant reduction of PVP (-13.8 ± 1.7%) but an increase in MAP (57.1 ± 2.2%) and TPR (101 ± 6%) from baseline, and there also was a cardiodepressant response (CI, -21.4 ± 2.3%). Infusion of TMP followed by TP induced significant reduction of PVP (-18.9 ± 1.4%) and CI (-11.9 ± 2.1%), but an increase in MAP (36.2 ± 2.5%) and TPR (55.0 ± 5.2%). Compared with vehicle followed by TP, TMP not only significantly enhanced portal hypotensive (PVP reduction) effects of TP but also attenuated the systemic pressor (MAP and TPR elevation) and cardiodepressant (CI reduction) effects of TP in both PVL and BDL rats. Our results suggest that TP, alone or in combination with TMP, induced portal hypotensive effects in two models of portal hypertensive rats. Combination of TP and TMP was beneficial in enhancing portal hypotensive effects of TP and ameliorating the systemic pressor and cardiodepressant effects of TP.Key words: terlipressin, tetramethylpyrazine, cirrhosis, portal hypertension, hemodynamics.

Effects of endothelin in portal hypertensive rats

1992 ◽  
Vol 83 (2) ◽  
pp. 165-170 ◽  
Author(s):  
Pi-Chin Yu ◽  
Jon-Son Kuo ◽  
Han-Chieh Lin ◽  
May C. M. Yang
Keyword(s):  
Blood Pressure ◽  
Portal Hypertension ◽  
Portal Vein ◽  
Venous Pressure ◽  
Portal Venous Pressure ◽  
Portal Vein Ligation ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Endothelin 1 ◽  
Sprague Dawley Rats

1. Effects of endothelin-1 on systemic arterial blood pressure, heart rate and portal venous pressure were compared in normal Sprague-Dawley rats and rats with portal hypertension induced by CCl4 and partial portal vein ligation. 2. Endothelin-1 produced biphasic effects on systemic blood pressure and portal venous pressure in all three groups of rats. However, the magnitude of the changes in blood pressure was less in portal hypertensive rats. 3. The ability of endothelin-1 to increase the portal venous pressure was also significantly diminished in portal hypertensive rats. On the other hand, the initial decrease in portal pressure was augmented in rats with partial portal vein ligation, and disappeared at higher dosage in CCl4-treated rats. 4. In accordance with the pressure recording in vivo, the dose-response vasoconstrictive activity of endothelin-1 was significantly attenuated in the intrahepatic vasculature. 5. The plasma immunoreactive endothelin concentration was significantly higher (5.55 ± 0.81 fmol/ml) in Sprague-Dawley rats than in CCl4-treated rats (2.83 ± 0.56 fmol/ml) and rats with partial portal vein ligation (2.68 ± 0.53 fmol/ml). 6. It was concluded that a lower plasma level of endothelin and a reduced vascular responsiveness may contribute, at least in part, to the hyperdynamics of portal hypertension.

Decreased vascular contractile and inositol phosphate responses in portal hypertensive rats

1995 ◽  
Vol 73 (3) ◽  
pp. 378-382 ◽  
Author(s):  
Yi-Tsau Huang ◽  
Chuang-Ye Hong ◽  
Pi-Chin Yu ◽  
Ming-Fang Lee ◽  
May C. M. Yang ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Contractile Response ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Venous Pressure ◽  
Portal Vein Ligation ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Contractile Responses ◽  
Tail Artery

The purpose of this study was to investigate the vascular contractile and inositol phosphate responses in portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation (PVL) in Sprague–Dawley rats. Sham-operated rats served as controls. Pressures, vasoconstrictor responses, and inositol phosphate responses were determined at 14 days after surgery. The portal venous pressure was significantly higher, while systemic arterial pressure and heart rate were lower, in PVL rats. Dose-dependent contractile responses were observed for both norepinephrine (1 × 10−8 – 3 × 10−6 M) and vasopressin (3 × 10−10 – 3 × 10−8 M) in the tail artery of both groups. The contractile response to norepinephrine was significantly decreased in PVL rats compared with controls at all doses. The contractile response to vasopressin was significantly decreased in PVL rats at higher doses. After myo-[3H]inositol incorporation in tail artery, the levels of 3H-labelled phosphatidylinositols (cpm/mg) were similar between the two groups. Norepinephrine (10−7 – 10−5 M) and vasopressin (10−10 – 10−8 M) dose dependently stimulated the 3H-labelled inositol phosphate production in the tail artery of both PVL and sham-operated rats. However, the response was significantly lower in PVL rats. The results suggested that the attenuation of vascular contractile responses in portal hypertension was reflected in the phosphoinositide messenger system.Key words: portal hypertension, inositol phosphates, phosphoinositide, tail artery, contractile response.

Role of thromboxane A2 in early BDL-induced portal hypertension

2003 ◽  
Vol 284 (3) ◽  
pp. G453-G460 ◽  
Author(s):  
Yukihiro Yokoyama ◽  
Hongzhi Xu ◽  
Nicole Kresge ◽  
Steve Keller ◽  
Amir H. Sarmadi ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Portal Pressure ◽  
Sham Operation ◽  
Sprague Dawley ◽  
Bicarbonate Buffer ◽  
Constant Flow Rate ◽  
Sprague Dawley Rats ◽  
Duct Ligation ◽  
Cox 2

Although the mechanisms of cirrhosis-induced portal hypertension have been studied extensively, the role of thromboxane A2 (TXA2) in the development of portal hypertension has never been explicitly explored. In the present study, we sought to determine the role of TXA2 in bile duct ligation (BDL)-induced portal hypertension in Sprague-Dawley rats. After 1 wk of BDL or sham operation, the liver was isolated and perfused with Krebs-Henseleit bicarbonate buffer at a constant flow rate. After 30 min of nonrecirculating perfusion, the buffer was recirculated in a total volume of 100 ml. The perfusate was sampled for the enzyme immunoassay of thromboxane B2(TXB2), the stable metabolite of TXA2. Although recirculation of the buffer caused no significant change in sham-operated rats, it resulted in a marked increase in portal pressure in BDL rats. The increase in portal pressure was found concomitantly with a significant increase of TXB2 in the perfusate (sham vs. BDL after 30 min of recirculating perfusion: 1,420 ± 803 vs. 10,210 ± 2,950 pg/ml; P < 0.05). Perfusion with a buffer containing indomethacin or gadolinium chloride for inhibition of cyclooxygenase (COX) or Kupffer cells, respectively, substantially blocked the recirculation-induced increases in both portal pressure and TXB2 release in BDL group. Hepatic detection of COX gene expression by RT-PCR revealed that COX-2 but not COX-1 was upregulated following BDL, and this upregulation was confirmed at the protein level by Western blot analysis. In conclusion, these results clearly demonstrate that increased hepatic TXA2 release into the portal circulation contributes to the increased portal resistance in BDL-induced liver injury, suggesting a role of TXA2 in liver fibrosis-induced portal hypertension. Furthermore, the Kupffer cell is likely the source of increased TXA2, which is associated with upregulation of the COX-2 enzyme.

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

1988 ◽  
Vol 254 (3) ◽  
pp. G322-G328 ◽  
Author(s):  
D. Kravetz ◽  
J. Bosch ◽  
M. T. Arderiu ◽  
M. P. Pizcueta ◽  
R. Casamitjana ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Portal Pressure ◽  
Portal Vein Ligation ◽  
Plasma Glucagon ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Systemic Hemodynamic ◽  
Blood Flows ◽  
Arteriolar Resistance ◽  
Regional Blood Flows

The effects of somatostatin infusion on splanchnic and systemic hemodynamics and plasma glucagon levels were investigated in rats with portal hypertension. Forty-four male Sprague-Dawley rats were studied. Portal hypertension was induced in 26 rats by partial portal vein ligation (PVL). These rats were divided in two experimental groups to receive blindly 1) somatostatin (PVL-SMT, n = 13) at a dose of 25 micrograms/kg body wt during 30 min preceded by a bolus injection of 15 micrograms/kg body wt or 2) placebo (saline) (PVL-P, n = 13) infused at the same rate as in the previous group. The remaining 18 rats were used as normal controls and received somatostatin (n = 9) or saline infusion (n = 9). Regional blood flows and cardiac output were measured using radioactive microspheres. Arterial and portal pressures were also measured. In portal hypertensive rats somatostatin infusion produced significant reductions in the increased portal venous inflow, reductions in portal pressure, and significantly increased portal venous resistance. Reduction of portal venous inflow was due to splanchnic vasoconstriction, evidenced by increased splanchnic arteriolar resistance. No significant differences were observed in systemic hemodynamic parameters between PVL-SMT and PVL-P rats. Plasma glucagon levels were significantly reduced by somatostatin to levels similar to those observed in sham-operated rats. In sham-operated rats, somatostatin also caused significant reduction in portal venous inflow and plasma glucagon concentration, although these changes were of lesser magnitude than in portal hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Extrahepatic angiogenesis hinders recovery of portal hypertension and collaterals in rats with cirrhosis resolution

2018 ◽  
Vol 132 (6) ◽  
pp. 669-683 ◽  
Author(s):  
Shao-Jung Hsu ◽  
Ming-Hung Tsai ◽  
Ching-Chih Chang ◽  
Yu-Hsin Hsieh ◽  
Hui-Chun Huang ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Portal Pressure ◽  
Treatment Strategies ◽  
Vascular Complications ◽  
Control Group ◽  
No Production ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Duct Ligation ◽  
Window Area

Liver cirrhosis is characterized by portal hypertension. However, the alteration of portal hypertension-related derangements during cirrhosis resolution is not well known. The present study aimed to establish animal models with cirrhosis resolution and to investigate the relevant changes during this process. Male Sprague–Dawley rats were applied. In reverse thioacetamide (rTAA) model, rats were randomly allocated into four groups with control, thioacetamide (TAA) cirrhosis and rTAA groups that discontinued TAA for 4 or 8 weeks after cirrhosis induction. In reverse bile duct ligation (rBDL) model, rats received choledochoduodenal shunt surgery upon the establishment of cirrhosis and 4, 8, or 16 weeks were allowed after the surgery. At the end, portal hypertension-related parameters were evaluated. Cirrhosis resolution was observed in rTAA groups. Portal pressure (PP) decreased after cirrhosis resolution but remained higher than control group (control, TAA, rTAA4, rTAA8 (mmHg): 5.4 ± 0.3, 12.9 ± 0.3, 8.6 ± 0.4, 7.6 ± 0.6). Further survey found the increased splanchnic blood flow did not reduce during cirrhosis resolution. The extrahepatic pathological angiogenesis was not ameliorated (% of mesenteric window area: 1.2 ± 0.3, 7.3 ± 1.1, 8.3 ± 1.0, 11.3 ± 2.7). In collateral system, the shunting degree reduced while the vessels structure remained. The vascular contractility of all systems and nitric oxide (NO) production were normalized. In rBDL series, PP decreased in rBDL16 groups but the extrahepatic angiogenesis persisted. In conclusion, cirrhosis resolution attenuates but not completely normalizes portal hypertension because of persistently high splanchnic inflow and angiogenesis. In clinical setting, vascular complications such as varices could persist after cirrhosis resolution and further investigation to define the follow-up and treatment strategies is anticipated.

Propranolol modulates the collateral vascular responsiveness to vasopressin via a Gα-mediated pathway in portal hypertensive rats

2011 ◽  
Vol 121 (12) ◽  
pp. 545-554 ◽  
Author(s):  
Jing-Yi Lee ◽  
Teh-Ia Huo ◽  
Hui-Chun Huang ◽  
Fa-Yauh Lee ◽  
Han-Chieh Lin ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Mrna Expression ◽  
Perfusion Pressure ◽  
Portal Pressure ◽  
Splenorenal Shunt ◽  
Portal Vein Ligation ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Propranolol Treatment ◽  
Pressure Changes

Gastro-oesophageal variceal haemorrhage is one of the most dreadful complications of portal hypertension and can be controlled with vasoconstrictors. Nevertheless, sympathetic tone abnormality and vascular hyporesponsiveness in portal hypertension may impede the haemostatic effects of vasoconstrictors. Propranolol, a β-blocker binding the G-protein-coupled adrenoceptor, is a portal hypotensive agent. However, whether propranolol influences the collateral vasoresponse is unknown. Portal hypertension was induced by PVL (portal vein ligation) in Sprague–Dawley rats. In an acute study with an in situ perfusion model, the collateral responsiveness to AVP (arginine vasopressin) was evaluated with vehicle, propranolol (10 μmol/l), propranolol plus suramin (100 μmol/l, a Gα inhibitor) or suramin pre-incubation. Gα mRNA expression in the splenorenal shunt, the most prominent intra-abdominal collateral vessel, was measured. In the chronic study, rats received DW (distilled water) or propranolol (10 mg·kg−1 of body weight·day−1) for 9 days. Then the concentration–response relationship of AVP and Gα mRNA expression were assessed. Propranolol pre-incubation elevated the perfusion pressure changes of collaterals in response to AVP, which was inhibited by suramin. The splenorenal shunt Gαq and Gα11 mRNA expression were enhanced by propranolol. The group treated with propranolol plus suramin had a down-regulation of Gα11 as compared with the propranolol group. Chronic propranolol treatment reduced mean arterial pressure, PP (portal pressure) and the perfusion pressure changes of collaterals to AVP. Gαs expression was up-regulated. In conclusion, propranolol pre-incubation enhanced the portal-systemic collateral AVP responsiveness in portal hypertensive rats, which was related to Gαq and Gα11 up-regulation. In contrast, the attenuated AVP responsiveness by chronic propranolol treatment was related to Gαs up-regulation. The Gα signalling pathway may be a therapeutic target to control variceal bleeding and PP in portal hypertension.

scholarly journals Glycyrrhizin Attenuates Portal Hypertension and Collateral Shunting via Inhibition of Extrahepatic Angiogenesis in Cirrhotic Rats

2021 ◽  
Vol 22 (14) ◽  
pp. 7662
Author(s):  
Chon Kit Pun ◽  
Hui-Chun Huang ◽  
Ching-Chih Chang ◽  
Chiao-Lin Chuang ◽  
Chun-Hsien Yen ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Portal Hypertension ◽  
Liver Fibrosis ◽  
Statistical Significance ◽  
Portal Pressure ◽  
Sham Operation ◽  
Sprague Dawley ◽  
Beneficial Effects ◽  
Duct Ligation ◽  
The Impact

Portal hypertension develops along with liver cirrhosis then induces the formation of portal-systemic collaterals and lethal complications. Extrahepatic angiogenesis plays an important role. Glycyrrhizin has been found to exhibit anti-angiogenic features, which leads to its extensive use. However, the relevant effects of glycyrrhizin on liver cirrhosis and portal hypertension have not been evaluated. This study thus aimed to investigate the impact of glycyrrhizin on portal hypertension-related derangements in cirrhotic rats. Male Sprague-Dawley rats received bile duct ligation (BDL) to induce cirrhosis or sham operation as control. The rats were subdivided to receive glycyrrhizin (150 mg/kg/day, oral gavage) or vehicle beginning on the 15th day post operation, when BDL-induced liver fibrosis developed. The effects of glycyrrhizin were determined on the 28th day, the typical timing of BDL-induced cirrhosis. Glycyrrhizin significantly reduced portal pressure (p = 0.004). The splanchnic inflow as measured by superior mesenteric arterial flow decreased by 22% (p = 0.029). The portal-systemic collateral shunting degree reduced by 30% (p = 0.024). The mesenteric angiogenesis and phospho-VEGFR2 protein expression were also downregulated (p = 0.038 and 0.031, respectively). Glycyrrhizin did not significantly influence the liver biochemistry data. Although glycyrrhizin tended to reverse liver fibrosis, statistical significance was not reached (p = 0.069). Consistently, hepatic inflow from portal side, hepatic vascular resistance, and liver fibrosis-related protein expressions were not affected. Glycyrrhizin treatment at the stage of hepatic fibrosis still effectively attenuated portal hypertension and portosystemic collateral shunting. These beneficial effects were attributed to, at least in part, the suppression of mesenteric angiogenesis by VEGF signaling pathway downregulation.

scholarly journals Diagnosis of sialodacryoadenitis virus infection of rats in a virulent enzootic outbreak

1981 ◽  
Vol 15 (4) ◽  
pp. 339-342 ◽  
Author(s):  
P. Carthew ◽  
R. P. Slinger
Keyword(s):  
Virus Infection ◽  
Antibody Response ◽  
Clinical Signs ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Natural Conditions ◽  
Breeding Colony ◽  
Serological Screening ◽  
Sprague Dawley Rats ◽  
Natural Outbreak

In a natural outbreak of sialodacryoadenitis virus it was observed that the incidence of clinical signs in spontaneous-hypertensive rats was 100%, and that these signs were of a severity not observed before in other strains of rats. Rats free of the virus were introduced so that the progress of the disease could be studied under natural conditions of spontaneous spread from the enzootically-affected breeding colony. The pathogenesis of the infection in these Sprague-Dawley rats has been recorded over a period of 10 days after their introduction to the colony, and the results of extensive serological screening have shown that the antibody response of the spontaneous-hypertensive rats to the virus is lower than in other strains of rat.

scholarly journals Elemental Mapping Of Bone Strontium In Rats Treated With Strontium Ranelate And Strontium Citrate Using 2D Micro-XRF And 3D Dual Energy K-edge Subtraction X-ray Imaging

2021 ◽  
Author(s):  
Daniel Arturo Cardenas
Keyword(s):  
Strontium Ranelate ◽  
Dual Energy ◽  
Therapeutic Effects ◽  
Sprague Dawley ◽  
Treatment Of Osteoporosis ◽  
3D Images ◽  
X Ray ◽  
X Ray Imaging ◽  
Sprague Dawley Rats ◽  
Animal Bones

Strontium-based medications, such as strontium ranelate, have been shown to have therapeutic effects in the treatment of osteoporosis, other strontium salts are assumed to have similar effects on bone health. The objective of this study was to compare the distribution of strontium in animal bones following administration of strontium ranelate and strontium citrate. Humerus bones were collected from female Sprague-Dawley rats that were dosed daily over ten weeks with strontium ranelate and strontium citrate, and no strontium (control). Bones were imaged using 2D micro-XRF and 3D dual energy KES X-ray imaging. The 2D imaging revealed differences in strontium and calcium levels between samples from treated and non-treated animals (푝 < 0.001). 3D images obtained showed that strontium was observed to be largely present in the trabecular regions under the epiphyseal plate with concentrations of approximately 5 to 15 mg/cm3 in the bones of both strontium treated groups. The thickness of the strontium layers below the growth plate in both the strontium ranelate and strontium citrate sample were not significantly different (푝 = 0.9201). Both imaging studies performed in this work showed that strontium from both salts is heterogeneously distributed in newly formed bone during treatment.

Ammonia reduction with ornithine phenylacetate restores brain eNOS activity via the DDAH-ADMA pathway in bile duct-ligated cirrhotic rats

2012 ◽  
Vol 302 (1) ◽  
pp. G145-G152 ◽  
Author(s):  
Vairappan Balasubramaniyan ◽  
Gavin Wright ◽  
Vikram Sharma ◽  
Nathan A. Davies ◽  
Yalda Sharifi ◽  
...  
Keyword(s):  
Bile Duct ◽  
Protein Expression ◽  
Ammonia Concentration ◽  
Sham Operation ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Duct Ligation ◽  
Tnf Α ◽  
No Signaling ◽  
Brain Water

Ammonia is central in the pathogenesis of hepatic encephalopathy, which is associated with dysfunction of the nitric oxide (NO) signaling pathway. Ornithine phenylacetate (OP) reduces hyperammonemia and brain water in cirrhotic animals. This study aimed to determine whether endothelial NO synthase activity is altered in the brain of cirrhotic animals, whether this is associated with changes in the endogenous inhibitor, asymmetric-dimethylarginine (ADMA) and its regulating enzyme, dimethylarginine-dimethylaminohydrolase (DDAH-1), and whether these abnormalities are restored by ammonia reduction using OP. Sprague-Dawley rats were studied 4-wk after bile duct ligation (BDL) ( n = 16) or sham operation ( n = 8) and treated with placebo or OP (0.6 g/kg). Arterial ammonia, brain water, TNF-α, plasma, and brain ADMA were measured using standard techniques. NOS activity was measured radiometrically, and protein expression for NOS enzymes, ADMA, DDAH-1, 4-hydroxynonenol (4HNE), and NADPH oxidase (NOX)-1 were measured by Western blotting. BDL significantly increased arterial ammonia ( P < 0.0001), brain water ( P < 0.05), and brain TNF-α ( P < 0.01). These were reduced significantly by OP treatment. The estimated eNOS component of constitutive NOS activity was significantly lower ( P < 0.05) in BDL rat, and this was significantly attenuated in OP-treated animals. Brain ADMA levels were significantly higher and brain DDAH-1 significantly lower in BDL compared with sham ( P < 0.01) and restored toward normal following treatment with OP. Brain 4HNE and NOX-1 protein expression were significantly increased in BDL rat brain, which were significantly decreased following OP administration. We show a marked abnormality of NO regulation in cirrhotic rat brains, which can be restored by reduction in ammonia concentration using OP.

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