6-ketoprostaglandin-f1-alpha and Hypertension--Portal

To study the mechanism involved in the potentially beneficial effect of ultra low dose aspirin (ULDA) in prehepatic portal hypertension, rats were pretreated with selective COX 1 or 2 inhibitors (SC-560 or NS-398 respectively), and subsequently injected with ULDA or placebo.. Portal hypertension was induced by portal vein ligation. Platelet activity was investigated with an in-vivo model of laser induced thrombus production in mesenteric circulation and induced hemorrhagic time (IHT). Platelet aggregation induced by ADP and dosing of prostanoid products 6-keto-PGF1alpha, TXB2, PGE2 and LTB4 were also performed.. The portal hypertensive group receiving a placebo showed a decreased in vivo platelet activity with prolonged IHT, an effect that was normalized by ULDA. SC-560 induced a mild antithrombotic effect in the normal rats, and an unmodified effect of ULDA. NS-398 had a mild prothrombotic action in portal hypertensive rats, similar to ULDA, but inhibited a further effect when ULDA was added. An increased 6-keto-PGF1alpha was observed in portal hypertensive group that was normalised after ULDA administration. TXA2 level after ULDA, remained unchanged.. These results suggest that the effect of ULDA on platelet activity in portal hypertensive rats, could act through a COX 2 pathway more than the COX 1, predominant for aspirin at higher doses.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aspirin; Blood Platelets; Cyclooxygenase Inhibitors; Dinoprostone; Disease Models, Animal; Dose-Response Relationship, Drug; Hypertension, Portal; Lasers; Leukotriene B4; Male; Nitrobenzenes; Platelet Activation; Pyrazoles; Rats; Rats, Wistar; Sulfonamides; Thrombosis; Thromboxane B2

To investigate the effects of prostacyclin (PGI(2)) and nitric oxide (NO) in the development of hyperdynamic circulatory state on chronic portal hypertensive rats.. Sixty-six male SD rats were divided into three groups, namely intrahepatic portal hypertension (IHPH) by injection of CCl(4), prehepatic portal hypertension (PHPH) by partial stenosis of the portal vein for 2 weeks and sham-operated controls (SO). Animals in each group were divided further into 3 subgroups and received N(omega)-nitro-L-arginine (L-NNA), indomethacin and saline (as control), respectively. Splanchnic and systemic hemodynamics was measured using radioactive microsphere techniques. The NO concentration in serum was determined by nitrates-nitrites which were measured using a colorimetric method, and concentration of PGI(2) was determined using specific radioimmunoassay for its stable hydrolytic product, 6-keto-PGF(1 alpha).. The concentrations of plasma 6-keto-PGF(1 alpha) and serum nitrates + nitrites in IHPH rats (1 123.85 +/- 153.64; 73.34 +/- 4.31) and in PHPH rats (891.88 +/- 83.11; 75.21 +/- 6.89) were significantly higher than those of SO rats (725.53 +/- 105.54;58.79 +/- 8.47). L-NNA and indomethacin could decrease the concentrations of plasma 6-keto-PGF(1 alpha) and serum nitrates + nitrites in IHPH and PHPH rats (P < 0.05). At the same time, CI, FPP and PVI were lowered while MAP, TPR and SVR were increased (P < 0.05). After deduction of NO action, there were no significant correlation between plasma PGI(2) level and hemodynamic parameters such as CI, TPR, PVI and SVR. However, after deduction of PGI(2) action, NO was still correlated highly with those hemodynamic parameters.. It is NO rather then PGI(2) that is a mediator in the formation and development of hyperdynamic circulatory state in chronic portal hypertensive rats.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Cyclooxygenase Inhibitors; Disease Models, Animal; Enzyme Inhibitors; Epoprostenol; Hemodynamics; Hypertension, Portal; Male; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; omega-N-Methylarginine; Random Allocation; Rats; Rats, Sprague-Dawley

Expression of constitutive and inducible cyclooxygenase (COX-1 and COX-2, respectively) and the role of prostanoids were investigated in the aorta and mesenteric vascular bed (MVB) from the portal vein-ligated rat (PVL) as a model of portal hypertension. Functional experiments were carried out in MVB from PVL and sham-operated rats in the absence or presence of the nonselective COX inhibitor indomethacin or the selective inhibitors of COX-1 (SC-560) or COX-2 (NS-398). Western blots of COX-1 and COX-2 proteins were evaluated in aorta and MVB, and PGI(2) production by enzyme immunoassay of 6-keto-PGF(1alpha) was evaluated in the aorta. In the presence of functional endothelium, decreased contraction to norepinephrine (NE) and increased vasodilatation to ACh were observed in MVB from PVL. Exposure of MVB to indomethacin, SC-560, or NS-398 reversed the hyporeactivity to NE and the increased endothelial vasodilatation to ACh in PVL, with NS-398 being more potent than the other two inhibitors. Upregulation of COX-1 and COX-2 expressions was detected in aorta and MVB from PVL portal hypertensive rats, and increased production of 6-keto-PGF(1alpha) was observed in aorta from portal hypertensive rats. These results suggest that generation of endothelial vasodilator prostanoids, from COX-1 and COX-2 isoforms, accounts for the increased mesenteric blood flow in portal hypertension.

Topics: 6-Ketoprostaglandin F1 alpha; Acetylcholine; Animals; Blotting, Western; Cyclooxygenase 1; Cyclooxygenase Inhibitors; Endothelium, Vascular; Hypertension, Portal; Isoenzymes; Male; Membrane Proteins; Norepinephrine; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Sprague-Dawley; Splanchnic Circulation; Vasoconstriction; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents

Despite the suppression of glucagon release, an adaptive response aimed at maintaining vasodilatation after octreotide treatment may exist in portal hypertension. The present study was undertaken to evaluate the possible interaction between endothelium and non-endothelium-derived vasodilators after 1-wk octreotide administration in cirrhotic rats. Rats were allocated to receive either vehicle or octreotide (30 or 100 microg/kg every 12 h subcutaneously). Hemodynamic values, plasma glucagon levels, endothelium-related vasodilatory activities, and aortic endothelial nitric oxide synthase (eNOS) expression were determined after treatment. Octreotide administration decreased plasma glucagon and increased serum 6-keto-PGF(1 alpha) and NOx levels without affecting the hemodynamic values. In cirrhotic rats receiving octreotide, there was a blunt response to either L-NAME or indomethacin administration alone, but this blunt pressor response disappeared after simultaneous administration of the two drugs. Additionally, an increased aortic eNOS expression was observed in cirrhotic rats receiving 1-wk octreotide. It is concluded that 1-wk octreotide treatment did not correct the hemodynamic derangement in cirrhotic rats. The enhanced endothelium-related vasodilatory activity was noted after octreotide treatment that overcame the octreotide-induced hemodynamic effects in portal hypertension.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aorta; Blotting, Western; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Enzyme Inhibitors; Glucagon; Hypertension, Portal; Indomethacin; Liver Cirrhosis; Male; NG-Nitroarginine Methyl Ester; Nitrates; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Nitrites; Octreotide; Rats; Rats, Sprague-Dawley; Somatostatin; Splanchnic Circulation; Vasoconstrictor Agents; Vasodilation

To observe the effects of sandostatin on gastric mucosal blood flow (GMBF) in rats with (portal hypertensive gastropathy, PHG) and its mechanisms.. Two weeks after portal vein ligation, the changes of systemic hemodynamics, GMBF, (portal vein pressure, PVP) were observed and plasma glucagon, plasma and gastric mucosal NO2-/NO3-, 6-Keto-PGF(1alpha) were measured after intravenous sandostatin, propranolol and normal saline.. GMBF and PVP were reduced after intravenous sandostatin or propranolol. Sandostatin decreased plasma glucagon, plasma and gastric mucosal NO2-/NO3-, and had no effect on MAP and heart rate of PHG rats as compared with control group of PHG. Propranolol had not these effects, but it might decrease MAP and heart rate. There were no differences of plasma and gastric mucosal 6-Keto-PGF(1alpha) between all PHG groups.. Sandostatin reduced GMBF of rats with PHG by hindering glucagon, NO, and had no effect on systemic hemodynamics.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Gastric Mucosa; Gastrointestinal Agents; Glucagon; Hypertension, Portal; Male; Nitric Oxide; Octreotide; Rats; Rats, Sprague-Dawley; Regional Blood Flow

Prostacyclin has been shown to play a role in hyperdynamic circulation in portal hypertension. Recently, a new subtype of cyclo-oxygenase (COX), COX-2, which acts as an inducible synthase in response to various stimuli. The aim of this study was to investigate whether COX-2 contributes to portal hypertension and whether a COX-2 blockade induces the same sort of gastric mucosal injury as a COX-1 blockade.. Portal hypertension (PHT) in rats was induced by a two-step ligation of the portal vein. The mean arterial pressure (MAP), portal pressure (PP), visceral blood flow volume (BFV), serum levels of 6-keto-prostaglandin F1alpha (PGF1alpha), thromboxane B2 (TXB2) and gastric mucosal injury induced by pure ethanol were all measured in PHT rats receiving different inhibitors (indomethacin, a highly selective COX-1 inhibitor; NS-398, a highly selective COX-2 inhibitor). Control rats treated by a sham operation were also studied.. The NS-398 administration significantly decreased PP to the same extent as indomethacin at doses of 5 and 10 mg/kg in PHT rats after a 60 min administration, while neither inhibitor affected the control rats. Both inhibitors significantly increased PP after a 30 min administration in the PHT and control rats at a dose of 5 mg/kg while both inhibitors significantly decreased PP after 60 min administration only in the PHT rats. Portal vein ligation treatment induced a significant increase in PP and BFV of the portal vein, gastric mucosa, oesophageal mucosa and the serum levels of 6-keto-PGF1alpha and TXB2, while portal vein ligation treatment induced a significant decrease in BFV of the liver. Both blockades increased MAP and decreased PP and BFV in the splanchnic area and decreased the serum level of 6-keto-PGF1alpha and TXB2 in the PHT rats, while neither blockade modified any parameters in the control rats, except that indomethacin administration significantly decreased the BFV of the gastric mucosa. Indomethacin administration significantly increased the ulcer index (UI). The NS-398 had no effect on UI in either the PHT or control rats. Only indomethacin significantly increased the number of rats demonstrating gastric mucosal long lesions (> 2 cm) in the PHT rats.. In the PHT rats, prostaglandin seemed to contribute to portal hypertension. Both COX blockades reduced PP and BFV of the portal vein and gastric mucosa. NS-398, a selective COX-2 inhibitor, may, therefore, improve portal hypertension without inducing gastric mucosal injury.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Ethanol; Gastric Mucosa; Hemodynamics; Hypertension, Portal; Indomethacin; Isoenzymes; Male; Membrane Proteins; Nitrobenzenes; Portal Pressure; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Sprague-Dawley; Regional Blood Flow; Sulfonamides; Thromboxane B2; Time

To evaluate the effects of nitric oxide inhibitor on prostacyclin (PGI2) biosynthesis and the role of PGI2 in hyperhemodynamics of portal hypertension.. Sprague Dawley rats were divided into four groups: intrahepatic portal hypertension (IHPH) by injection of CCl4, prehepatic portal hypertension (PHPH) by stenosis of the portal vein, end-to-side portacaval shunt (PCS), and sham-operated controls (SO). Animals of each group were subdivided into 2 groups: systemic administration of nitric oxide inhibitor L-NMMA and vehicle. The radioactive microsphere method was used for hemodynamic study. The level of plasma PGI2 (6-keto-PGF1 alpha) was measured by radioimmunoassay.. The characteristics of hyperdynamic circulatory state including increased cardiac output and splanchnic blood flow, decreased mean arterial blood pressure, total peripheral vascular resistance, and splanchnic vascular resistance were observed in IHPH, PHPH and PCS rats. The magnitude of hyperhemodynamics was in the order of PCS > PHPH > IHPH rats. The hyperdynamic circulatory state in IHPH, PHPH and PCS rats could be effectively reversed by L-NMMA to the baseline values of hemodynamics in SO rats. The baseline concentrations of plasma 6-keto-PGF1 alpha (ng/ml) in PHPH, IHPH, PCS, and SO rats were 6.93 +/- 2.43, 5.09 +/- 2.27, 2.36 +/- 1.01 and 1.56 +/- 0.61, respectively. The concentrations of plasma 6-Keto-PGF1 alpha in PHPH, IHPH and PCS rats were significantly higher than those in SO rats. Moreover, the concentrations were significantly higher in PHPH and IHPH rats than in PCS rats (P < 0.05). After administration of L-NMMA, the concentrations of plasma 6-Keto-PGF1 alpha (ng/ml) in PHPH, IHPH, PCS and SO rats were 7.69 +/- 2.98, 5.68 +/- 2.66, 5.50 +/- 0.79, 5.02 +/- 2.86, respectively. As compared to the baseline value, the concentrations of 6-keto-PGF1 alpha rats were slightly increased in IHPH, PHPH rats (P > 0.05), but significantly increased in PCS and SO rats (P < 0.05).. In this study, the hyperdynamic circulatory state in portal hypertensive rats and portacaval shunt rats was completely reversed by L-NNMA to normal, but the level of 6-keto-PGF1 alpha was still elevated. The results indicate that PGI2 is not involved in hyperhemodynamics of portal hypertension.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Carbon Tetrachloride Poisoning; Enzyme Inhibitors; Epoprostenol; Hemodynamics; Hypertension, Portal; Male; Nitric Oxide Synthase; omega-N-Methylarginine; Portacaval Shunt, Surgical; Rats; Rats, Sprague-Dawley

To evaluate the role of increased portal pressure and portosystemic shunting in elevated level of prostacyclin (PGI2) in portal hypertension.. Thirty-six male Sprague-Dawley rats were divided into four groups: prehepatic portal hypertension (PHPH, 8 rats), intrahepatic portal hypertension (IHPH, 9), end-to-side portacaval shunt (PCS, 8), and sham-operated controls (SO, 11). Two weeks after surgery, free portal pressure (FPP) was measured; systemic and splanchnic hemodynamics was studied by radioactive microsphere technique and blood sample from the femoral artery was obtained to measure the level of plasma 6-keto-PGF1 alpha with radioimmunoassay.. The FPP (mmHg) in IHPH, PHPH, PCS and SO rats was 13.10 +/- 1.02, 12.10 +/- 1.52, 3.0 +/- 0.82 and 6.86 +/- 0.69, respectively. The value of FPP was significantly increased in IHPH, PHPH rats and significantly decreased in PCS rats when compared to SO rats. Cardiac index (CI) and portal venous inflow (PVI) were in the order of PCS > PHPH > IHPH > SO rats. Portosystemic shunting (PSS) in PCS, PHPH, IHPH was 99.7 +/- 0.29%, 76.02 +/- 20.62% and 30.34 +/- 10.18%, respectively. The concentrations of plasma 6-keto-PGF1 alpha (ng/ml) in PHPH, IHPH, PCS and SO rats were 6.93 +/- 2.43, 5.09 +/- 2.27, 2.36 +/- 1.01 and 1.56 +/- 0.61, respectively. The concentrations of plasma PGI2 in PHPH, IHPH and PCS rats were significantly higher than those in SO rats. Furthermore, the concentrations of plasma PGI2 in PHPH and IHPH rats were also significantly higher than those in PCS rats. Moreover, a closed positive correlation existed between plasma PGI2 and FPP (r = 0.67, P < 0.001).. The results of the present study suggest that the elevated PGI2 in portal hypertension is mainly due to the overproduction of PGI2 in vascular epithelium cells induced by increased portal pressure, whereas portosystemic shunting and liver dysfunction play a secondary role. In addition, the results of this study do not support that PGI2 mediated the hyperhemodynamics in portal hypertension.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Endothelium, Vascular; Epoprostenol; Hypertension, Portal; Male; Portasystemic Shunt, Surgical; Rats; Rats, Sprague-Dawley

Plasma levels and gastric mucosal contents of prostaglandin (PG) E2 and prostacyclin were determined in cirrhotic patients with portal hypertensive gastropathy (PHG), in cirrhotic patients without PHG and in healthy controls. PGE2 and 6-keto-PGF1 alpha (a stable metabolite of prostacyclin) levels were measured in 30 cirrhotic patients and 10 controls, using radioimmunoassay. Of 30 cirrhotics, 13 had PHG of the fundus and the corpus. Plasma concentrations of 6-keto-PGF1 alpha in the cirrhotic patients were significantly higher than in the controls (p < 0.01), but there was no significant difference between cirrhotics and controls with regard to plasma levels of PGE2. The gastric mucosal contents of 6-keto-PGF1 alpha in the fundus was significantly higher in cirrhotics with PHG than those without PHG (p < 0.05) and controls (p < 0.01). However, the gastric mucosal contents of PGE2 in the fundus were not significantly different in cirrhotics with and without PHG. The gastric mucosal contents of 6-keto-PGF1 alpha significantly correlated to the plasma levels (r = 0.37, p < 0.05), but there was no significant correlation between plasma levels and gastric mucosal contents of PGE2. Since prostacyclin has vasodilator and gastric acid inhibitory effects, we speculate that high contents of prostacyclin in the gastric mucosa may have some role in the pathogenesis of PHG.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Dinoprostone; Female; Gastric Fundus; Gastric Mucosa; Humans; Hypertension, Portal; Japan; Liver Cirrhosis; Male; Middle Aged; Stomach Diseases

Although prostaglandins are thought to be involved in the hyperdynamic circulation of portal hypertension, the role of this substance has not been elucidated. Dose-response curves, the hemodynamic effects of prostacyclin (20 micrograms/kg) and its inhibitor indomethacin and measurements of plasma and urinary levels of 6-keto-prostaglandin F1 alpha were compared in three groups of six rats each: normal, with portal vein stenosis and with secondary biliary cirrhosis. Plasma and urinary levels of 6-keto-prostaglandin F1 alpha were higher in rats with portal vein stenosis and cirrhotic rats than in normal rats. Dose-response curves showed similar maximal decreases in arterial pressure in the three groups, whereas the maximal increase in portal pressure was less marked in cirrhotic rats than in normal rats and rats with portal vein stenosis. In normal rats, prostacyclin increased cardiac output by 21% and portal pressure by 41%. Similar increases were observed in rats with portal vein stenosis. In contrast, prostacyclin did not affect cardiac output and portal pressure in cirrhotic rats. Indomethacin induced a more marked vasoconstrictive effect in normal rats than in cirrhotic rats. This study shows that prostacyclin plays a role in the hemodynamic alterations in portal hypertension. Moreover, the hyporeactivity observed in cirrhotic rats suggests that prostacyclin plays a major role in the circulatory changes of portal hypertension due to chronic liver disease.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Pressure; Cardiac Output; Common Bile Duct; Dose-Response Relationship, Drug; Epoprostenol; Heart Rate; Hemodynamics; Hypertension, Portal; Indomethacin; Kidney; Liver Cirrhosis, Biliary; Male; Portal System; Portal Vein; Rats; Rats, Sprague-Dawley; Regional Blood Flow; Renal Circulation; Vascular Resistance

Many organs have the capacity to form prostanoids. Under pathophysiological conditions the biosynthesis of TXB2 and 6-oxo-PGF1 alpha is markedly increased in the myocardium and the gastric mucosa. Tumor growth is linked with an enhanced prostanoid formation. Furthermore a rise of the PG content could be found in the liquor, aqueous humor and urine under diseases of the related organs. These results could be of some significance for diagnosis and therapy control.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aqueous Humor; Brain Diseases; Child; Gastric Mucosa; Gastritis; Guinea Pigs; Heart Diseases; Humans; Hypertension, Portal; In Vitro Techniques; Indomethacin; Kidney Transplantation; Myocardium; Skin Neoplasms; Thromboxane B2

The total body production of prostacyclin was shown to be increased in cirrhotic patients, suggesting that its synthesis by blood vessels of the systemic circulation is enhanced. However, the mechanism by which the synthesis of systemic prostacyclin is stimulated is not known. The present study investigated the urinary excretion of 2,3-dinor-6-keto-PGF1 alpha, an index of total body prostacyclin synthesis, first, in cirrhotics with portal hypertension (n = 19) as compared with cirrhotics with reduced portal pressure after portacaval shunt surgery (n = 18) and with control noncirrhotic subjects (n = 11), and; second, in cirrhotics before and after intestinal decontamination by oral nonabsorbable antibiotics (n = 9 antibiotic treated patients, n = 10 control nontreated cirrhotics). Control noncirrhotic subjects showed lower urinary excretion of 2,3-dinor-6-keto-PGF1 alpha than both groups of cirrhotics (P less than 0.001). Interestingly, urinary excretion of 2,3-dinor-6-keto-PGF1 alpha was significantly higher in cirrhotics with portacaval shunt than in those with portal hypertension (P less than 0.01). The urinary excretion of 2,3-dinor-6-keto-PGF1 alpha decreased significantly after intestinal decontamination in the antibiotic-treated group (580.1 +/- 232.4 vs. 431.2 +/- 219.2 pg/mg creatinine; P less than 0.05) but not in nontreated patients (543.9 +/- 214.4 vs. 581.2 +/- 281.4 pg/mg creatinine; P = NS). These data suggest that the increased urinary excretion of 2,3-dinor-6-keto-PGF1 alpha observed in cirrhotics is not directly related to portal hypertension itself but to portal blood factors that bypass the liver. Some such factors may be of intestinal bacterial origin.

Topics: 6-Ketoprostaglandin F1 alpha; Anti-Bacterial Agents; Bacteria; Epoprostenol; Humans; Hypertension, Portal; Intestines; Liver Cirrhosis; Portacaval Shunt, Surgical

The possibility that prostacyclin could be a systemic hormone and could mediate the splanchnic hyperemia of chronic portal hypertension was evaluated in rabbits in a normotensive state and in rabbits with chronic partial ligation of the portal vein. In rabbits with portal hypertension (PHT), 6-keto-prostaglandin F1 alpha (PGF1 alpha, a prostacyclin degradation product) was elevated twofold in all vascular beds (systemic arterial, systemic venous, and portal venous) when compared with levels in control animals. In PHT rabbits, exogenous prostacyclin infusion after cyclooxygenase blockade through the systemic arterial, systemic venous, or portal venous route resulted in an equal elevation of 6-keto-PGF1 alpha in the reciprocal vascular beds and restored the original precyclooxygenase blockade hemodynamics. These hemodynamic changes were of equal magnitude irrespective of site of infusion in PHT. In controls there was no significant change in 6-keto-PGF1 alpha or hemodynamics with intraportal infusion. We conclude that prostacyclin achieves systemic levels by escaping hepatic degradation resulting from portosystemic shunting in the animal with chronic portal hypertension.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aorta, Abdominal; Epoprostenol; Hypertension, Portal; Indomethacin; Mesenteric Arteries; Portal Vein; Portasystemic Shunt, Surgical; Rabbits; Vascular Resistance; Vena Cava, Inferior

We studied generation of prostaglandins E2 and 6-keto F1a by surface epithelial cell isolated from the gastric mucosa of portal hypertensive and sham-operated rats. Oxygenated cell suspensions containing 80 +/- 3% of surface epithelial cells were incubated for 30 min at 37 degrees C and the concentration of prostaglandin E2 and 6-keto-prostaglandin F1a in medium was measured by radioimmunoassay. Viability of the cells was assessed with Fast green exclusion at baseline and after 30-min and 60-min incubation. Within 30 minutes the surface epithelial cells obtained from portal hypertensive rats generated 22.0 +/- 1.6 (mean +/- SE) pg prostaglandin E2 and 40.7 +/- 4.7 pg 6-keto prostaglandin F1a, per 10(6) cells. These were significantly less than prostaglandin generation by cells obtained from sham-operated rats. The viability of the surface epithelial cells from portal hypertensive rats was also significantly reduced compared with sham-operated rats after 60 minute incubation. Reduced ability of the surface epithelial cells to generate prostaglandins may be one mechanism for increased susceptibility of portal hypertensive gastric mucosa to injury by noxious agents.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Cell Survival; Dinoprostone; Epithelium; Gastric Mucosa; Hypertension, Portal; Male; Rats; Rats, Inbred Strains

The prevalence of pulmonary hypertension among patients with portal hypertension, especially following a shunt operation, is significantly higher than that of primary pulmonary hypertension, suggesting the hypothesis that large portasystemic shunt plays a major role in development of pulmonary hypertension. To support this hypothesis, I studied experimentally the hemodynamic changes and the pathological findings in lung in 97 rats killed between one and 24 months after portasystemic shunt operations. The right ventricular systolic pressure (RVSP) and the right ventricular wall thickness were significantly high in the 82 rats raised over 3 months after the operations. In these rats the pathological findings in the lung revealed a thickness of pulmonary arterioles with medial hypertrophy, concentric intimal proliferation, and plexiform lesions. The values of endotoxin in central venous blood were significantly high and related with RVSP and shunt ratio. In pulmonary venous blood, thromboxane B2 increased and 6-keto PGF1a decreased. In conclusion, some of the rats developed pulmonary hypertension fter receiving a portasystemic shunt operation. It is suspected that endotoxin passing through the shunt plays a role in the development of pulmonary hypertension.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arterioles; Blood Pressure; Collateral Circulation; Endotoxins; Hypertension, Portal; Hypertension, Pulmonary; Lung; Male; Portasystemic Shunt, Surgical; Pulmonary Circulation; Rats; Rats, Inbred Strains; Thromboxane B2

The object of this study was to investigate clinical conditions in which increased production of prostacyclin (PGI2) has been reported. 6-Oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha) is the stable hydrolysis product of PGI2 and was measured in plasma from patients undergoing hepatic or cardiac surgery and in unoperated patients with vascular and hepatic disease, using gas chromatography/mass spectrometry. Blood obtained simultaneously from portal and peripheral veins, during emergency surgery for bleeding oesophageal varices in six patients with cirrhosis of the liver, contained very high concentrations of 6-oxo-PGF1 alpha (range 99-11,485 pg/ml of plasma). 6-Oxo-PGF1 alpha was higher in portal than in peripheral blood in five out of six patients. Six unoperated patients with cirrhosis and oesophageal varices which were not bleeding all had normal peripheral plasma concentrations of 6-oxo-PGF1 alpha less than 2 pg/ml (normal up to 5 pg/ml). Seventeen patients with severe vascular disease had normal basal plasma 6-oxo-PGF1 alpha concentrations (less than 2 pg/ml). Eighteen subjects with atheromatous coronary artery disease underwent aorta-coronary artery grafting, and plasma concentrations of 6-oxo-PGF1 alpha were markedly elevated during surgery (range 55-1207 pg/ml). We conclude that surgery stimulates PGI2 production substantially, and argue that the function of PGI2 may be to limit intravascular extension of thrombus from sites of haemostasis. Inappropriate PGI2 synthesis may contribute to the massive haemorrhage characteristic of oesophageal variceal bleeding.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Cardiopulmonary Bypass; Coronary Disease; Epoprostenol; Esophageal and Gastric Varices; Humans; Hypertension, Portal; Middle Aged; Vascular Diseases

Portal hypertension was produced experimentally in rats by partial constriction of the portal vein. Twelve rats were injected daily with indomethacin, 4 mg/kg body weight, and 12 with the vehicle (80% ethanol, 0.5 ml/day). There were no differences in portal-systemic shunts nor systemic or splanchnic haemodynamics between indomethacin-treated and untreated rats. These results suggest that cyclo-oxygenase products do not play a significative role in haemodynamic alterations shown by portal-ligated rats.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Dinoprostone; Hemodynamics; Hypertension, Portal; Indomethacin; Prostaglandins E; Rats; Renin; Splanchnic Circulation