Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hemodynamic effects of long-term (3 months) treatment with enalapril, a potent angiotensin converting enzyme inhibitor, were studied in 12 randomly selected patients with portal hypertension and a previous episode of hemorrhage from esophageal varices. All these patients underwent injection sclerotherapy of varices at 1-week intervals. As a control group 13 patients treated only with injection sclerotherapy and placebo were used. After 3 months the wedged hepatic venous pressure (25.5 +/- 4.8 vs. 21.3 +/- 4.8 mmHg) and the non-wedged hepatic venous pressure gradient (17.0 +/- 6.0 vs. 12.6 +/- 3.4 mmHg) were significantly lower than the basal values (p < 0.01) in the group treated with enalapril. A large decrease (> 3 mmHg) in these pressures was observed only in 50% of the patients. In the group treated with sclerotherapy+placebo this pressure reduction was not observed. Systemic hemodynamics and liver function tests did not change during the treatment. None of our patients died during the study or the next 6 months. We conclude that enalapril lowers portal pressure in patients with portal hypertension, although not in all of them, and may be used to good effect to manage patients with esophageal varices in combination with sclerotherapy.
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PMID:Effect of enalapril treatment and sclerotherapy of esophageal varices on hepatic hemodynamics in portal hypertension. 133 75

We have previously shown that angiotensin converting enzyme inhibitor enalapril causes a potent decrease in portal pressure gradient, but only in about one half of patients with portal hypertension and an episode of bleeding esophageal varices in patient's history. Twenty-one consecutive patients after first episode of bleeding from esophageal varices were enrolled in the trial. Patients were treated by sclerotherapy in combination with enalapril. The level of ACE in patients with portal hypertension (10.4, SD 4.5) was significantly higher than in normal population (4.5, SD 1.3 mu kat/l-1) [p < 0.001]. After 3 months treatment decreased ACE to normal or subnormal levels in all 21 patients (2.9, SD 1.5 mu kat.l-1) [p < 0.001], but simultaneously measured hepatic venous pressure gradient decreased more than 3 mm Hg only in 11 (52%). No correlation between changes of portal pressure gradient and changes of ACE concentrations were found. We conclude that patients with portal hypertension have significantly higher serum ACE level with a large decrease after enalapril, but it is not possible to predict the effect of enalapril on portal pressure by estimation of ACE level in serum in individual patient.
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PMID:[Is it possible to predict a decrease in portal pressure after administration of ACE inhibitors?]. 818 70

The objective of pharmacotherapy of portal hypertension is to reduce the portal pressure and the subsequent reduction of pressure and blood flow in the oesophageal varicosities in patients with portal hypertension. Pharmacological treatment is used in acute bleeding from oesophageal varices where it is a very useful first step for arresting haemorrhage and it does not require any special training or complicated equipment. Pharmacotherapy holds its place also in primary and secondary prophylaxis of oesophageal variceal bleeding. In particular a combination of pharmacotherapy with sclerotherapy is useful to reduce the occurrence of early recurrent bleeding. Among hitherto known vasoactive drugs the following ones are used most frequently: vasopressin, terlipressin, somatostatin, beta-blockers, nitrates and ACE inhibitors. Other drugs influencing portal haemodynamics are the subject of research.
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PMID:[Pharmacologic treatment of portal hypertension]. 897 62

A posthepatitic cirrhotic patient may undergo elective or urgent abdominal operation for an extra-hepatic or hepatic disease. According to the high postoperative morbidity (61%), surgery is indicated only for symptomatic or complicated cholelithiasis. A surgical procedure for refractory ascites has been devised to create a permanent peritoneo-venous shunt by a one way pressure-sensitive valve (Leveen). The procedure is simple and brings a long lasting relief with recovery in strength and nutrition and improved kidney function. Sclerotherapy is widely used to treat acute variceal bleeding while repeated sclerotherapy is used in the long-term management to eradicate varices. When indicated, liver transplantation is the best treatment to prevent variceal bleeding recurrence. Also portosystemic shunts effectively prevent recurrent variceal bleeding. They are, however, major operations with an important morbidity and mortality, particularly in poor risk patients. The most advocated shunts today are the Warren distal splenorenal shunt and the Sarfeh portacaval shunt using a small diameter prosthetic H-graft. The transjugular intrahepatic portosystemic stent-shunt (TIPSS) is a new treatment for portal hypertension and its complications. From a haemodynamic point of view it allows balanced hepatic perfusion. Postoperative mortality is rare; further bleeding and encephalopathy are reasonably acceptable. The most relevant complications concern dislocation of the prosthesis, stenosis and thrombosis of the shunt, which can be corrected by non-invasive dilatation. Encephalopathy is the main complication of surgical portosystemic shunts. It is usually controlled by protein diet restriction, and administration of lactulose or oral antibiotics. In severe forms the patients may be treated by an oesophageal transection with oesophagogastric devascularization, and by a postoperative suppression of the portosystemic shunt using external maneuvers. Posthepatitic liver cirrhosis is frequently complicated by the onset of an hepatocellular carcinoma. Early detection (aFP, DCP, Echography) and curative resection are the best ways to improve long term prognosis. Segmentectomy achieves a good balance between liver function preservation and radical exeresis for tumours less than 5 cm in diameter. Liver transplantation may be considered for the treatment of long-staging cirrhotic patients in whom hepatocarcinoma development has been recognized at an early presymptomatic stage. Hepatic arterial chemoembolization (gelfoam, lipiodol, mitomycin C or doxorubicin) may improve the survival of patients with unresectable malignant disease of the liver. A marked reduction in liver size may occur in the weeks following an effective chemoembolization with objective (CT scan) and subjective improvement (amelioration of specific symptoms). Liver chemoembolization is absolutely contraindicated in the presence of jaundice disordered liver function (Child C) or complete portal venous obstruction. In the last years, the number of patients treated by liver transplantation has greatly increased. Surgical technique, postoperative management, and immunosuppressive therapy account for the dramatic improvement of the results. However, indications for selection of patients and the timing for liver transplantation are still not well defined.
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PMID:[Surgical approach to posthepatitic cirrhotic patient today]. 927 83

The therapy of portal hypertension depends to a significant extent on its clinical manifestation. In cases of acute haemorrhage from oesophageal varices in patients with portal hypertension, the objective of the therapy is to stop the haemorrhage (endoscopically, or by compression by means of a balloon probe) and to decrease the pressure and the reflux within the portal vascular bed. Urgent sclerotisation under the simultanous pharmacologic decrease of portal hypertension is successful in 93-95%. There is an alternative procedure residing in introducing a balloon probe for several hours and subsequent repeated sclerotisation until a complete eradication of varices is achieved regarding the prevention of haemorrhage exacerbation. Urgent surgical solution is on the basis of the results of various investigated studies reserved for patients in whom endoscopic sclerotisation was not successful. Indication of surgical therapy must be also deliberated in candidates for liver transplantation, regarding the possible consequent technical problems after some types of interventions. Endoscopic sclerotisation of oesophageal varices is also an appropriate preparation for transplantation of the liver in patients with liver cirrhosis included into the transplantation programme. TIPS is a perspective new method in the therapy of portal hypertension of both, non-bleeding varices, as well as in other indications. It is also a certain intermediating link in therapy in some patients with liver cirrhosis on the waiting list of candidates for liver transplantation. Pharmacotherapy is a significant part of the portal hypertension therapy. It is appropriate to combine the endoscopic treatment with pharmacotherapy of portal hypertension in both, cases of acute haemorrhage, as well as in the prevention of haemorrhage exacerbation. In cases of acute haemorrhage, the combination of glypressin with nitroglycerin is justified, as well as the therapy by somatostatin. The prevention of haemorrhage exacerbations uses a whole series of vasoactive substances, especially nitrates, beta-blockers and ACE inhibitors. The prevention of the first bleeding includes the prophylactic therapy (endoscopic, pharmacologic, or surgical) recommended only in a selected group of patients under high risk of bleeding. The possible perspective option will reside especially in the combined pharmacological therapy, the fact of which will have to be proven in the future. (Fig. 1, Ref. 25.)
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PMID:[Treatment of portal hypertension]. 958 83

The clinical course of patients with cystic fibrosis (CF) with functionally similar mutations in the CF transmembrane conductance regulator gene is variable and must therefore relate to secondary genetic and environmental factors. We examined the hypothesis that polymorphisms of certain inflammatory mediator and regulatory genes affect clinical outcome by influencing the degree of end-organ damage. By studying the possible association between clinical outcome and angiotensin I-converting enzyme (ACE) and cytokine genotypes by amplification refractory mutation system-polymerase chain reaction, using stored DNA from 261 white patients with CF, we found that ultrasound features of cirrhosis occurred more frequently in patients with the high-producer (DD) rather than the low-producer (II) ACE genotype (odds ratio [95% confidence interval], 3.7 [1.2 to 12]). Moreover, significant pulmonary dysfunction (age at which FEV1 < 50%) was associated with the high-producer ACE genotype (2.3 [1.2 to 4.5]) and transforming growth factor-beta1 genotype (2.6 [1.0 to 6.8]) as well as with age at first colonization with Pseudomonas aeruginosa (9.1 [1.1 to 72]). We conclude that the high-producer ACE genotype predicts patients with CF who have an increased chance of developing portal hypertension; and high-producer ACE and TGF-beta1 genotypes are secondary genetic factors contributing to pulmonary dysfunction in these patients.
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PMID:End-organ dysfunction in cystic fibrosis: association with angiotensin I converting enzyme and cytokine gene polymorphisms. 1255 16

Arterial Hypertension (AH) is characterized by reduced nitric oxide (NO) biosynthesis, activation of the Renin-Angiotensin-Aldosteron-System (RAAS), vasoconstriction, and microvascular rarefaction. The latter contributes to target organ damage, especially in left ventricular hypertrophy, and may partially be due to impaired angiogenesis. Angiogenesis, the formation of new microvessels and microvascular networks from existing ones, is a highly regulated process that arises in response to hypoxia and other stimuli and that relieves tissue ischemia. In AH, angiogenesis seems impaired. However, blood pressure alone does not affect angiogenesis, and microvascular rarefaction is present in normotensive persons with a family history for AH. Normal or increased NO in several processes and diseases enables or enhances angiogenesis (e.g. in portal hypertension) and reduced NO biosynthesis (for example, in a rat model of AH, in other disease models in vivo, and in endothelial NO Synthase knock out mice) impairs angiogenesis. Angiogenic growth factors such as Vascular Endothelial Growth Factor (VEGF) and Fibroblast Growth Factor (FGF) induce NO and require NO to elicit an effect. Effector molecules and corresponding receptors of the RAAS either induce (Bradykinin, Angiotensin II) or perhaps inhibit angiogenesis. The pattern of Bradykinin- and Angiotensin II-receptor expression and the capacity to normalize NO biosynthesis may determine whether ACE-inhibitors, Angiotensin II-receptor antagonists and other substances affect angiogenesis. Reconstitution of a normally vascularized tissue by reversal of impaired angiogenesis with drugs such as ACE inhibitors and AT1 receptor antagonists may contribute to successful treatment of hypertension-associated target organ damage, e.g. left ventricular hypertrophy.
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PMID:Hypertension and angiogenesis. 1287 Dec 5

We report a case of decompensated porto-pulmonary hypertension closely associated with the development of intra-portocaval shunt thrombosis. A woman with Laennec's cirrhosis was hospitalized because of severe dyspnea and edema. She underwent surgical portocaval anastomosis ten years ago. Imaging studies showed massive intra-shunt thrombosis, portal hypertension, ascites, pleuro-pericardial effusions and enlargement of right cardiac cavities. Cardiac catheterization allowed to rule out coronary and left-sided heart abnormalities and led to the diagnosis of pre-capillary pulmonary hypertension. Antithrombotic treatment with low molecular weight heparin was instituted. The management also included ACE inhibitors, spironolactone, low-salt diet and lactulose. The patient was discharged and three months later we observed the disappearance of edema, ascites and pleuro-pericardial effusions, a marked body weight reduction and improved dyspnea and liver function tests. A possible link between the development of intra-shunt thrombosis and clinical decompensation in our patient was hypothesized. In fact, it has been demonstrated that the increased portal pressure, caused by occlusion of portosystemic shunt, reduces renal plasma flow and increases systemic endothelin-1 concentration. In our patient the disappearance of edematous state and improved dyspnea observed after recanalization of the shunt strongly support this hypothesis.
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PMID:Decompensated porto-pulmonary hypertension in a cirrhotic patient with thrombosis of portocaval shunt. 1808 Dec 37

Idiopathic portal hypertension (IPH) is characterized by non-cirrhotic presinusoidal intrahepatic portal hypertension. The etiopathogenesis of the disease is poorly understood. Obliteration with microthrombosis of the small portal vein branches may lead to lesions underlying portal hypertension. We aimed to put forward a comprehensive thrombophilic mutation profile in IPH and its probable contribution to pathogenesis. Eleven patients and 12 controls were included. We used the CVD-StripAssay which is based on the reverse-hybridization principle to identify a total of 12 thrombophilic gene mutations: Factor V R506Q, Factor V H1299R, prothrombin G20210A, Factor XIII V34L, beta-Fibrinogen -455 G-A, PAI-1 4G/5G, platelet GPIIIa L33P, MTHFR C677T, MTHFR A1298C, ACE I/D, Apo B R3500Q and Apo E2/E3/E4, respectively. We also evaluated some blood parameters and protein C, protein S, AT-III levels using commercially available assays. IPH patients and controls were similar in respect to gender distribution (P = 1.000). Mean age was 31.2 in patients and 29.1 in controls (P = 0.622). Pica history was present in 54.5% of the patients. Mean protein C and AT-III levels were lower in patients than that of controls (P = 0.002 and 0.001, respectively). Factor XIII V34L, PAI-1, GPIIIa L33P, MTHFR C677T and MTHFR A1298C frequencies of genetic polymorphisms were found to be significantly higher among patients than that of controls. Apolipoprotein E2/E3/E4 analysis showed an inverse relationship with IPH when E2 plus E4 compared with E3. A higher frequency of Beta-Fibrinogen -455G-A mutation was observed in patients, but this difference did not reach a statistical significance. Our data represent the most comprehensive study to date with respect to thrombophilic gene polymorphisms in IPH. The data support a possible pathogenetic role in IPH, at least by some of the prothrombotic mutations. In order to confirm or refuse this proposal, a larger cohort of patients is needed.
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PMID:Analysis of inherited thrombophilic mutations and natural anticoagulant deficiency in patients with idiopathic portal hypertension. 1868 11

Portal hypertension is the most common complication of chronic liver diseases, such as cirrhosis. The increased intrahepatic vascular resistance seen in hepatic disease is due to changes in cellular architecture and active contraction of stellate cells. In this article, we review the historical aspects of the kallikrein-kinin system, the role of bradykinin in the development of disease, and our main findings regarding the role of this nonapeptide in normal and experimental models of hepatic injury using the isolated rat liver perfusion model (mono and bivascular) and isolated liver cells. We demonstrated that: 1) the increase in intrahepatic vascular resistance induced by bradykinin is mediated by B2 receptors, involving sinusoidal endothelial and stellate cells, and is preserved in the presence of inflammation, fibrosis, and cirrhosis; 2) the hepatic arterial hypertensive response to bradykinin is calcium-independent and mediated by eicosanoids; 3) bradykinin does not have vasodilating effect on the pre-constricted perfused rat liver; and, 4) after exertion of its hypertensive effect, bradykinin is degraded by angiotensin converting enzyme. In conclusion, the hypertensive response to BK is mediated by the B2 receptor in normal and pathological situations. The B1 receptor is expressed more strongly in regenerating and cirrhotic livers, and its role is currently under investigation.
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PMID:Portal hypertensive response to kinin. 1972 13


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