Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Essential hypertension is associated with endothelial dysfunction, which is caused mainly by the production of oxygen-free radicals that can destroy nitric oxide (NO), and impair its beneficial and protective effects on the vessel wall. In prospective studies, endothelial dysfunction is associated with increased incidence of cardiovascular events. Antihypertensive drugs show contrasting effects in terms of improvement or restoration of endothelial function. Little evidence is available with beta-blockers. Whereas treatment with atenolol has a negative effect in peripheral subcutaneous and muscle microcirculation, insufficient evidence is available to establish whether new compounds such as nebivolol, which activates the L-Arginine--NO pathway, and carvedilol, which has strong antioxidant activity, can improve endothelial function in patients with hypertension. Calcium channel antagonists, particularly the dihydropyridines, can reverse impaired endothelium-dependent vasodilation in different vascular districts, including the subcutaneous, epicardial, renal and forearm circulation. However, conflicting results are found in the brachial artery. In the forearm circulation, nifedipine and lacidipine can improve endothelial dysfunction by restoring NO availability through a mechanism probably related to an antioxidant effect. ACE inhibitors, on the other hand, seem to improve endothelial function in subcutaneous, epicardial, brachial and renal circulation, whereas they are ineffective in potentiating the blunted response to acetylcholine in the forearm of patients with essential hypertension. They can also selectively improve endothelium-dependent vasodilation to bradykinin, an effect not mediated by restoring NO availability but probably related to hyperpolarisation. Recent evidence suggests angiotensin II AT(1)-receptor antagonists can restore endothelium-dependent vasodilation to acetylcholine in subcutaneous microcirculation but not in that of the forearm muscle. Evidence concerning the effect of these drugs on the brachial artery in patients with atherosclerosis is positive. However, treatment with an AT(1)-receptor antagonist can improve basal NO release and decrease the vasoconstrictor effect of endogenous endothelin-1. In conclusion, despite the considerable evidence that impaired endothelium-dependent vasodilation can be improved by appropriate antihypertensive treatment, no clinical data exist demonstrating that the reversal of endothelial dysfunction is associated with a reduction in cardiovascular events. In the near future, large scale clinical trials are required to demonstrate that treatment of endothelial dysfunction can lead to better prognosis in patients with essential hypertension.
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PMID:Effects of antihypertensive drugs on endothelial dysfunction: clinical implications. 1181 73

OBJECTIVE: To investigate the changes of the markers of pulmonary vascular endothelial cells (PVECs) after acute lung injury (ALI) induced by bone marrow extract (BME) injection in rabbits. METHODS: Thirty-one rabbits were randomized into control (CG, n=10) and experimental groups (EG, n=21). The rabbits in EG were injected with homogeneous bone marrow extract (0.35 ml/kg, 2 ml/h) at a slow and continuous rate through the jugular vein to establish the model of ALI. At 6 h after the injection, the number of circulating endothelial cells (CECs) in the blood, contents of granule membrane protein-140 (GMP-140), angiotensin converting enzyme (ACE) and endothelin-1 (ET-1) in the plasma and the content of GMP-140 in the pulmonary tissue were determined at various time intervals. Then the animals were killed and routine pathological examination and electron microscopy were performed to observe the changes in the pulmonary tissue. RESULTS: The levels of plasma GMP-140, ACE, ET-1 and CECs were significantly increased in the early stage (0.5 h) and remained higher for 6 h. The marked increase of plasma GMP-140 (3.25 times) in the early stage was negatively correlated to PaO(2), but positively to other parameters. IHC-staining showed that the GMP-140 on the surface of PVECs became weak. CONCLUSIONS: BME injection at slow and continuous rate can establish an acceptable model of ALI. Determination of plasma GMP-140 might be an important measure for the early surveillance and the evaluation of prognosis of ALI in clinical management of serious traffic accidents.
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PMID:Changes in pulmonary vascular endothelial cells after acute lung injury induced by bone marrow extract injection in rabbits. 1187 53

The aim of the study was to examine whether the circulating cell adhesion molecules, von Willebrand factor (vWf) and endothelin-1, are elevated in patients with essential hypertension with no other risk factors for atherosclerosis and thus may serve as a markers of endothelial dysfunction in uncomplicated hypertension. Furthermore, the effect of treatment with the ACE inhibitor, quinapril, on levels of endothelial dysfunction markers were studied. The levels of adhesion molecules (intercellular cell adhesion molecule-1 [ICAM-1], E-selectin, P-selectin), von Willebrand factor (vWf) and endothelin-1 were measured in patients with hypertension without any other risk factors of atherosclerosis before and after treatment with quinapril (n = 22) and in normotensive controls (n = 22). Compared with normotensive subjects, the hypertensive patients had significantly higher levels of ICAM-1 (238 vs 208 ng/ml, P = 0.02), vWf (119 vs 105 IU/dl, P < 0.05) and endothelin-1 (5.76 vs 5.14 fmol/ml, P < 0.05). Three-month treatment of hypertensive patients with quinapril led to a significant decrease in the levels of endothelin-1 (5.76 vs 5.28 fmol/ml, P < 0.01). We did not observe significant changes in the levels of adhesion molecules and vWf after ACE inhibitor treatment, although a trend toward a decrease was apparent with all these parameters. Patients with uncomplicated hypertension with no other risk factors of atherosclerosis had significantly elevated levels of ICAM-1, vWf, and endothelin-1. Our data suggest that these factors may serve as markers of endothelial damage even in uncomplicated hypertension. In hypertensive patients, treatment with the ACE inhibitor quinapril resulted in a significant decrease in endothelin-1 levels. These findings indicate a beneficial effect of ACE inhibitors on endothelial dysfunction in hypertensive patients.
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PMID:Circulating intercellular cell adhesion molecule-1, endothelin-1 and von Willebrand factor-markers of endothelial dysfunction in uncomplicated essential hypertension: the effect of treatment with ACE inhibitors. 1214 57

The inhibition of angiotensin II through angiotensin converting enzyme inhibitors or angiotensin receptor blockers has become the foundation of medical treatment of progressive chronic renal disease. Although these drugs provide a significant improvement over earlier treatments, they only slow the progression of renal disease, implying the need for additional drugs that could be combined with antiangiotensin treatment. Potentially valuable novel drug targets include downstream mediators of angiotensin II such as transforming growth factor-b, plasminogen activator inhibitor-1, and endothelin-1. In addition, recent evidence points to aldosterone as a major player in progressive renal disease, indicating that multiple points of the renin-angiotensin-aldosterone system might have to be targeted. This paper reviews the experimental and clinical evidence indicating that targeting these cytokines and hormones could provide additional benefits to antiangiotensin treatment in chronic renal disease.
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PMID:Angiotensin II and progressive renal insufficiency. 1221 60

Endothelial dysfunction and remodeling of the vessel wall of large and small arteries is associated with hypertension and other risk factors for cardiovascular disease. These changes alter vascular function and mechanics, aggravate high blood pressure (BP), and may accelerate the progression of atherosclerosis. Activation of oxidative stress by angiotensin II is a key component of this process. Angiotensin II stimulates nicotinamide adenine dinucleotide phosphate (NADPH)/nicotinamide adenine dinucleotide (NADH) oxidase in endothelium, smooth muscle cells, and the adventitia of blood vessels to generate reactive oxygen species, leading to endothelial dysfunction, growth, and inflammation. Upregulation of endothelin-1, adhesion molecules, nuclear factor-kappaB, and other inflammatory mediators, as well as increased breakdown of nitric oxide and uncoupling of nitric oxide synthase, contribute to the progression of vascular disease and atherogenesis. Clinical studies in which treatment with angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) was used demonstrated correction of some of the changes in large and small arteries in hypertensive subjects, whereas identical BP lowering with beta-blockers had no effect on endothelial function. In experimental models of atherosclerosis, ARBs, including losartan potassium, valsartan, and olmesartan medoxomil, have demonstrated the ability to prevent the progression of atherosclerosis. This was in part associated with decreased expression of inflammatory mediators and improved endothelial function. Blockade of the renin-angiotensin-aldosterone system with ACE inhibitors or ARBs appears to blunt both the development and progression of vascular disease in both small and large vessels in experimental models and in humans beyond the effect of these agents on BP. This may help to explain the positive results of recently completed trials such as Heart Outcomes Prevention Evaluation (HOPE) and Losartan Intervention for Endpoint Reduction in Hypertension (LIFE).
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PMID:Beyond blood pressure: the endothelium and atherosclerosis progression. 1238 92

The objective of the investigation was to assess whether circulating adhesion molecules, von Willebrand factor (vWf) and endothelin-1 are elevated in patients with mild uncomplicated essential hypertension without further risk factors of atherosclerosis and whether they could serve as indicators of endothelial dysfunction in this form of hypertension. Furthermore the authors investigated the effect of ACE inhibitor treatment (ACEI), quinapril, on the level of these markers of endothelial dysfunction. The level of adhesion molecules [intercellular cytoadhesion molecule-1 (ICAM-1), E-selectin, P-selectin], von Willebrand s factor (vWf) and endothelin-1 were assessed in patients with mild essential hypertension without further cardiovascular risk factors or clinical manifestations of atherosclerosis before and after quinapril treatment (n = 25) and compared with normotensive controls (n = 29). The results of the examinations provided evidence that contrary to controls the hypertensive subjects had significantly higher ICAM-1 levels (237.8 vs. 207.8 ng/ml, P = 0.02) vWf (118 vs. 106 IU/dl, p < 0.05) and endothelin-1 (5.81 vs. 5.15 fmol/ml, p < 0.05). Three-month treatment of hypertensive patients with ACEI led to a significant drop of endothelin-1 levels (5.81 vs. 5.26 fmol/ml, p = 0.01). The authors proved also an unequivocal declining trend of other cytoadhesion molecules and vWf after ACEI treatment, the changes however were not statistically significant. From the investigation it may be concluded that also patients with uncomplicated essential hypertension without other cardiovascular risk factors or clinical manifestations of atherosclerosis have significantly elevated plasma levels of ICAM-1, vWf and endothelin-1. Higher concentrations of these factors suggest endothelial dysfunction already in mild forms of essential hypertension without further risk factors or cardiovascular complications. A significant drop of endothelin-1 and declining trend of the other investigated indicators suggest that ACEI treatment can favourably influence endothelial dysfunction in hypertensive patients also independently on reduction of the BP.
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PMID:[Is mild essential hypertension without obvious organ complications and risk factors associated with increased levels of circulating markers of endothelial dysfunction? Effect of ACE inhibitor therapy]. 1242 1

There is evidence that angiotensin II (Ang II) and endothelin-1 (ET-1) may interact in an additive or synergistic way during luteal regression. The aim of the study was to investigate real time changes in luteal tissue of angiotensin and endothelin system members in mRNA expression, tissue concentrations, tissue localization, and ACE (angiotensin converting enzyme) antagonist application after prostaglandin F(2alpha) (PG) induced (days 8-12) luteal regression in cow. Corpora lutea (CL) were collected by transvaginal ovaryectomy before and 2, 4, 12, 24, 48, and 64 hr (n = 5/time point) after PG injection. ACE mRNA expression (RT-PCR) increased continuously and peaked at 12, 24 hr; ECE-1 (endothelin converting enzyme) peaked at 12 hr, and both peptides in tissue (Ang II and ET-1) increased significantly and peaked at 24 hr. The expression of receptors for Ang II (AT1R and AT2R) did not change in contrast to ET receptors (ETR-A and ETR-B), which were up-regulated. Localization in tissue revealed very weak staining for Ang II and ET-1 before PG application followed by a clear increase of staining predominantly in large luteal cells, but also in endothelial cells. In two experiments, the attempt was made to block ACE by the antagonist captopril with two different doses. In both experiments with captopril, progesterone levels were not significantly different from controls. Ang II alone seems to be not essential for functional luteolysis in bovine system. In conclusion, the results suggest that both Ang II and ET-1 are in parallel up-regulated during luteal regression and may act as vasoconstrictors during functional luteolysis, but also as apoptosis inducer during functional/structural luteolysis.
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PMID:Real-time changes of the local vasoactive peptide systems (angiotensin, endothelin) in the bovine corpus luteum after induced luteal regression. 1265 34

The influence of estrogen on the regulation of cardiovascular function remains a controversial and complex area of investigation. We assessed the effects of estrogen depletion in the congenic mRen(2). Lewis rat, established from the back-cross of the original (mRen2)-27 transgenic onto the Lewis inbred strain. Ovariectomy of heterozygous mRen(2). Lewis at 4 to 5 weeks resulted in a progressive increase in blood pressure compared with the sham surgery congenics at weeks 6 to 11. At 11 weeks, the ovariectomized mRen(2). Lewis (OVX) systolic blood pressure averaged 195+/-3.7 mm Hg versus 141+/-4.0 mm Hg for sham. Plasma Angiotensin (Ang) II, serum ACE activity, plasma renin concentration, as well as urinary excretion of Ang II, 8-isoprostane F2alpha, and endothelin-1 were elevated; however, renal mRNA levels of eNOS were suppressed after ovariectomy. Estrogen replacement reduced blood pressure below both the sham and OVX by 11 weeks (125+/-2.9 mm Hg, n=7, P<0.01 versus OVX and sham). Moreover, the AT1 receptor antagonist olmesartan (CS866; week 12 to 16) essentially normalized blood pressure to 113+/-5.4 mm Hg (n=6, P<0.01 versus OVX and sham). The attenuation of the hypertension was still evident 7 weeks after complete withdrawal of treatment (124+/-4.1 mm Hg at week 23). In summary, the OVX mRen.2. Lewis exhibited a rapid and sustained increase in blood pressure. Estrogen or olmesartan lowered pressure by a similar extent. We conclude that the ovary exerts considerable influence on the regulation of the blood pressure in the mRen2. Lewis strain, possibly by limiting activation of the renin-angiotensin system.
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PMID:Estrogen or the AT1 antagonist olmesartan reverses the development of profound hypertension in the congenic mRen2. Lewis rat. 1287 87

A total of 172 patients with cardiac failure (CF) of functional class II-IV aged 46-62 years were studied. Clinical condition of the patients was stabilized by the conventional therapy including ACE inhibitor--enalapril in a dose 10-20 mg/day. In 3 weeks this therapy was combined with losartan in a dose 25-50 mg/day. The course of treatment was 48 weeks. Cardiodynamics was assessed by duplex echocardiography and dopplerography. Plasmic concentrations of atrial sodiumuretic peptide (ASUP), renin, angiotensin-II, aldosteron, norepinephrine, epinephrine, serotonin, hydrocortisone, endothelin-1 were measured with radioimmunoassay. In the study group there were 31 deaths for 48 weeks. ASUP concentration in the deceased was significantly higher than in the survivors (n = 141). The stepwise regression analysis discovered correlation between plasmic ASUP and end-diastolic volume of the left ventricle (r = 0.62; p = 0.01), dopplerographic index (r = 0.52; p = 0.001), left ventricular ejection fraction (r = -0.66; p = 0.002), velocity of early diastolic filling (r = -0.84; p = 0.001), plasmic pool of norepinephrine (r = 0.66; p = 0.001), endotheline-1 (r = 0.70; p = 0.03) and angiotensin-II (r = 0.55; p = 0.02), daily dose of furosemide (r = 0.80; p = 0.001), heart rate (r = 0.64; p = 0.02). The strongest negative effect on CF patients' survival was linked with plasmic content of ASUP (relative risk = 4.55), angiotensin-II (RR = 3.2), ejection fraction < 25% (RR = 3.02). Thus, elevation of ASUP in blood plasm can be regarded a marker of a high cardiovascular risk of CF patients treated with AT-antagonist.
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PMID:[Prognostic value of elevation of plasma concentration of atrial natriuretic peptide in patients with cardiac failure. Results of a cohort study]. 1468 5

High-altitude pulmonary oedema (HAPE) is a potentially fatal condition affecting fit and previously well individuals at altitudes in excess of 3000 m. This article discusses the mechanisms of HAPE, considers the contribution of hypoxic pulmonary vasoconstriction and alterations in sodium transport to the pathological process. It discusses the various biochemical mediators such as nitric oxide (NO), endothelin-1 (ET-1), and the renin-angiotensin-aldosterone system (RAS) that may be involved and considers possible oxygen-sensing mechanisms involved in hypoxic adaptation such as hypoxia-inducible factor-1 (HIF-1). Those who have had HAPE once run an unpredictable but significant risk of recurrence; therefore, there may be a constitutional or genetic component in its aetiology. This paper considers the possible involvement of genes that may be involved in physiological adaptation to hypoxia (e.g., angiotensin-1 [AT(1)]-converting enzyme [ACE], tyrosine hydroxylase, serotonin transporter [5-HTT], and endothelial NO synthase [eNOS] genes). As yet, no formal association has been identified between an identified genetic polymorphism and HAPE, but genetic variation provides a possible mechanism to explain interindividual variation in response to hypoxia and enhanced or reduced performance at altitude.
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PMID:The genetic basis of high-altitude pulmonary oedema. 1476 4


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