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)

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.

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.

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.

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.

scholarly journals Dual Angiotensin Receptor and Neprilysin Inhibitor Ameliorates Portal Hypertension in Portal Hypertensive Rats

Pharmaceutics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 320
Author(s):  
Shao-Jung Hsu ◽  
Hui-Chun Huang ◽  
Chiao-Lin Chuang ◽  
Ching-Chih Chang ◽  
Ming-Chih Hou ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Portal Pressure ◽  
Saline Control ◽  
Portal Vein Ligation ◽  
Angiotensin Receptor ◽  
Hypertensive Rats ◽  
Neprilysin Inhibitor ◽  
Hepatic Histology

Background: Portal hypertension is characterized by exaggerated activation of the renin-angiotensin-aldosterone axis. Natriuretic peptide system plays a counter-regulatory role, which is modulated by neprilysin. LCZ696 (sacubitril/valsartan) is a dual angiotensin receptor and neprilysin inhibitor. This study evaluated the effect of LCZ696 on portal hypertensive rats. Methods: Portal hypertension was induced by partial portal vein ligation (PVL) in rats. LCZ696, valsartan (angiotensin receptor blocker), or normal saline (control) was administered in PVL rats for 10 days. Then, hemodynamic and biochemistry data were obtained. The hepatic histology and protein expressions were surveyed. On the parallel groups, the portal-systemic shunting degrees were determined. Results: LCZ696 and valsartan reduced mean arterial pressure and systemic vascular resistance. LCZ696, but not valsartan, reduced portal pressure in portal hypertensive rats (control vs. valsartan vs. LCZ696: 15.4 ± 1.6 vs. 14.0 ± 2.3 vs. 12.0 ± 2.0 mmHg, control vs. LCZ696: P < 0.05). LCZ696 and valsartan improved liver biochemistry data and reduced intrahepatic Cluster of Differentiation 68 (CD68)-stained macrophages infiltration. Hepatic endothelin-1 (ET-1) protein expression was downregulated by LCZ696. The portal-systemic shunting was not affected by LCZ696 and valsartan. Conclusion: LCZ696 and valsartan reduced mean arterial pressure through peripheral vasodilation. Furthermore, LCZ696 significantly reduced portal pressure in PVL rats via hepatic ET-1 downregulation.

Bile acids do not mediate the hyperdynamic circulation in portal hypertensive rats

1990 ◽  
Vol 259 (1) ◽  
pp. G21-G25 ◽  
Author(s):  
P. Genecin ◽  
J. Polio ◽  
L. A. Colombato ◽  
G. Ferraioli ◽  
A. Reuben ◽  
...  
Keyword(s):  
Blood Flow ◽  
Portal Hypertension ◽  
Mean Arterial Pressure ◽  
Bile Acids ◽  
Portal Pressure ◽  
Control Group ◽  
Portal Vein Ligation ◽  
Hypertensive Rats ◽  
Hyperdynamic Circulation ◽  
Portosystemic Shunting

Portal hypertension is accompanied by hyperdynamic systemic and splanchnic circulation. Serum bile acids (BAs), which are elevated in portal hypertension and have vasodilatory properties, have been proposed as mediators of this hyperdynamic circulation. In this study, portal hypertensive rats [accomplished by partial portal vein ligation (PVL)] were gavaged with cholestyramine (PVL-CH) to decrease circulating BA levels. A control group of rats was gavaged with an inert suspension of Metamucil (PVL-ME). The following hyperdynamic parameters were found to be similar in PVL-CH and PVL-ME: mean arterial pressure (119 +/- 6 vs. 124 +/- 5 mmHg), portal pressure (13.2 +/- 0.6 vs. 14.5 +/- 0.5 mmHg), cardiac index (0.33 +/- 0.04 vs. 0.34 +/- 0.03 ml.min-1.g body wt-1), splanchnic blood flow (1.4 +/- 0.13 vs. 1.6 +/- 0.1 ml.min-1.g body wt-1), portosystemic shunting (82 +/- 8 vs. 92 +/- 3%), peripheral arteriolar resistances (344 +/- 74 vs. 387 +/- 29 mmHg.min.ml-1.g body wt), and splanchnic arteriolar resistances (75 +/- 14 vs. 72 +/- 6 mmHg.min.ml-1.g splanchnic wt; 1,471 +/- 150 vs. 1,325 +/- 120 mmHg.min.ml-1.g body wt). BA in PVL-ME (84 +/- 9 microM/l) were similar to those previously observed in untreated PVL and significantly greater than those measured in PVL-CH (25 +/- 4 microM/l; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of continued NO inhibition on portal hypertensive syndrome after portal vein stenosis in rat

1994 ◽  
Vol 267 (6) ◽  
pp. G984-G990 ◽  
Author(s):  
J. C. Garcia-Pagan ◽  
M. Fernandez ◽  
C. Bernadich ◽  
P. Pizcueta ◽  
J. M. Pique ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Portal Vein ◽  
Portal Pressure ◽  
Continuous Treatment ◽  
Portal Vein Ligation ◽  
Sprague Dawley ◽  
Portal Vein Stenosis ◽  
No Inhibition ◽  
Arteriolar Resistance ◽  
Lower Cardiac Output

The present study investigated whether chronic nitric oxide (NO) inhibition prevents the hyperdynamic circulatory syndrome that appears in rats after partial portal vein ligation (PPVL). N omega-nitro-L-arginine methyl ester (L-NAME; 30 micrograms.kg-1.min-1, n = 17), a NO biosynthesis inhibitor, or vehicle (n = 17) was infused continuously from PPVL through subcutaneously osmotic pumps. Studies were performed, in ketamine-anesthetized Sprague-Dawley rats, in one-half of the animals at 4 days and in the remaining one-half at 8 days from PPVL. At 4 days, PPVL rats treated with L-NAME had higher mean arterial pressure (MAP), systemic vascular resistance (SVR), and splanchnic arteriolar resistance (SAR) and lower cardiac output and portal venous inflow (PVI) than PPVL rats treated with vehicle (P < 0.05). Similarly, at 8 days PPVL rats treated with L-NAME had higher MAP and SVR and lower cardiac output (P < 0.05) than PPVL rats treated with vehicle. In contrast, PVI and SAR were similar. At 4 days plasma volume and mesenteric-systemic shunting were lower, although nonsignificantly, in PPVL rats treated with L-NAME. This trend completely disappeared at 8 days. L-NAME did not change portal pressure at either 4 or 8 days. After 4 days of continuous treatment with L-NAME, nonportal hypertensive control rats had a significantly higher MAP, lower cardiac index and PVI, and higher SVR and SAR than nonportal hypertensive rats treated with vehicle. Contrary to PPVL rats, these effects were maintained after 8 days of treatment. The present study shows that NO contributes to the systemic disturbances of portal hypertension. However, NO inhibition delayed but did not prevent the splanchnic vasodilation that appears after PPVL, suggesting that other factors could also be involved.

scholarly journals A Novel Method of Determining Portal Systemic Shunting using Biodegradable 99TCm Labelled Albumin Microspheres

HPB Surgery ◽  
1995 ◽  
Vol 8 (4) ◽  
pp. 223-229 ◽  
Author(s):  
J. Yates ◽  
D. M. Nott ◽  
P. J. Maltby ◽  
D. Billington ◽  
J. N. Baxter ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Portal Vein ◽  
Portal Pressure ◽  
Repeated Measurements ◽  
Control Group ◽  
Portal Vein Ligation ◽  
Hypertensive Rats ◽  
Albumin Microspheres ◽  
Novel Method

Portal systemic shunting (PSS) and portal pressure were measured in control rats and in animals with portal hypertension induced by partial portal vein ligation (PPVL). The portal pressure in rats with partial portal vein ligation (13.4 ± 0.5 mm.Hg.) was significantly higher (p < 0.005) than in the control group (9.6 ± 0.6 mm.Hg.). Portal systemic shunting measured by consecutive injections of radiolabelled methylene diphosphonate (MDP), a non-diffusable marker and albumin microspheres directly into the splenic pulp was significantly increased (P < 0.005) in the portal hypertensive animals (30.8 ± 2.5%) compared to sham operated rats (2.6 ± 1.5%). Similarly, in portal hypertensive rats portal systemic shunting measured by intrasplenic injections of radiolabelled cobalt microspheres (37.1 ± 3.9%) was significantly greater (p < 0.005) than in control animals. There was a good correlation and agreement (r = 00.97) between the two methods of measuring portal systemic shunting. However because the 99Tcm-albumin microspheres are biodegradable the method allows portal systemic shunting to be measured in man. Furthermore since the computer adjusts the baseline to zero after each determination of portal systemic shunting the methodology allows repeated measurements to be made.

Phosphorylation of eNOS initiates excessive NO production in early phases of portal hypertension

2002 ◽  
Vol 282 (6) ◽  
pp. H2084-H2090 ◽  
Author(s):  
Yasuko Iwakiri ◽  
Ming-Hung Tsai ◽  
Timothy J. McCabe ◽  
Jean-Philippe Gratton ◽  
David Fulton ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Specific Activity ◽  
Ex Vivo ◽  
Active Form ◽  
Initial Increase ◽  
No Production ◽  
Portal Vein Ligation ◽  
Sprague Dawley ◽  
Perfusion Studies

Akt, also known as protein kinase B, is a serine/threonine kinase. Akt becomes active when phosphorylated by the activation of receptor tyrosine kinases, G protein-coupled receptors, and mechanical forces such as shear stress. Studies in vitro have shown that Akt can directly phosphorylate endothelial nitric oxide (NO) synthase (eNOS) and activate the enzyme, leading to NO production. The aim of this study was to test the hypothesis that the phosphorylation of eNOS plays a role in the enhanced NO production observed in early portal hypertension. Male Sprague-Dawley rats were subjected to either sham or portal vein ligation (PVL), and mesenteric arterial beds were used for ex vivo perfusion studies. Mesenteric arterial beds from PVL rats had an approximately 60–70% decrease in response to methoxamine (an α1-agonist and vasoconstrictor) compared with the sham group ( P < 0.01). When N G-monomethyl-l-arginine (a NOS inhibitor) was added to the perfusion, the difference in perfusion pressure between the two groups was abolished, suggesting that enhanced NO production in the PVL group blunted the response to the vasoconstrictor. The reduced responsiveness in PVL was not due to changes in eNOS expression but was due to an increase in enzyme-specific activity, suggesting posttranslational modification of eNOS. The phosphorylation of eNOS at Ser1176 was significantly increased by twofold ( P < 0.05) in the PVL group. Furthermore, PVL significantly increased Akt phosphorylation (an active form of Akt) by threefold ( P< 0.05). When vessels were treated with wortmannin (10 nM) to block the phosphatidylinositol-3-OH-kinase/Akt pathway, NO-induced vasodilatation was significantly reduced. These results suggest that the phosphorylation of eNOS by Akt activates the enzyme and may be the first step leading to an initial increase in NO production in portal hypertension.

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