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)

To evaluate platelet activation thromboxane A2 (TxA2) and beta-thromboglobulin (beta TG) were used as markers and in addition we studied the biosynthesis of prostacyclin. Synthesis of TxA2 and prostacyclin was assessed by measurement of urinary metabolites. Fifteen untreated hypertensive patients (HT) and 15 age-matched normotensive controls (NT) were investigated at rest, during and after exercise. HT patients were re-examined after 3 months on enalapril. During basal conditions there was no difference in the excretion of Tx-M, PGI-M or beta TG between the groups. During strenuous exercise HT exhibit a significantly higher increase in prostacyclin synthesis (162%) compared to NT (76%). The levels of beta TG increased with 82% in the HT and 24% in the NT group, Tx-M increased with 27% and 23% respectively. Treatment with the ACE-inhibitor enalapril did not significantly alter these findings. These results indicate that there is no evidence of basal platelet activation in early essential hypertension. Strenuous exercise leads to some increase in Tx-M in both groups, with no pronounced differences between the groups. Hypertensive patients exhibit a significantly increased prostacyclin response to exercise which could be due to differences in vessel-wall reactivity. Enalapril seems to exert no effect on platelet activation or on prostacyclin biosynthesis.
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PMID:Platelet activation and prostacyclin release in essential hypertension. 141 May 27

The effect of various antihypertensive medications on platelet function is of increasing interest. Conflicting effects of captopril on platelet function are reported and the impact of angiotensin converting enzyme (ACE) inhibitors not containing a sulfhydryl group such as enalapril, lisinopril, and quinapril on platelet function remains unstudied. Therefore, the aim of the present study was to examine the effect of antihypertensive treatment with quinapril, a novel ACE inhibitor not containing a sulfhydryl group, on platelet function. Ten white men (age range of 32-61 years) with untreated mild-to-moderate essential hypertension (supine diastolic blood pressure greater than 95 mm Hg) were treated with 4 weeks each of placebo and quinapril in a double-blind, randomized, crossover design. Quinapril (20 mg twice a day) significantly lowered systolic (p less than 0.01) and diastolic blood pressure (p less than 0.01) without any significant effect on heart rate or plasma catecholamines. No significant change was noted for in vitro platelet aggregation induced by epinephrine, ADP, or collagen. Plasma concentrations of the platelet release factors beta-thromboglobulin and platelet factor 4 did not change, nor did the platelet content of norepinephrine, platelet weight (mg/10 ml of blood), circulating platelet count, or platelet size. Thus, as assessed by a broad spectrum of platelet parameters, we found that antihypertensive treatment with quinapril has no significant effect on platelet function in patients with mild-to-moderate essential hypertension. These "platelet-neutral" properties of quinapril suggest that quinapril, both from a thromboembolic and a hemostatic point of view, may be a rather safe agent for treatment of hypertension.
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PMID:Platelet function during antihypertensive treatment with quinapril, a novel angiotensin converting enzyme inhibitor. 170 46

The renin-angiotensin system is the major contributor to development of hypertension, atherosclerosis, and many other cardiovascular diseases. Angiotensin II, one of the main effectors of this system, contributes to the pathogenesis of hypertension and plays an important role in monocyte, platelet, and endothelium interactions. The effects on platelet and endothelial function, either by angiotensin converting enzyme inhibitors or angiotensin receptor antagonists, are still not well understood. A double-blind, randomized, prospective trial of either enalapril (10-20 mg daily) or eprosartan (400-800 mg daily) over a 10-week period was conducted in 42 patients (27 males, 15 females). Platelet activation was evaluated by measuring platelet factor 4 (PF-4), beta-thromboglobulin (beta-TG), the ratio of platelet factor 4 to beta-thromboglobulin, and endothelial function by measuring total plasma nitrate levels, von Willebrand factor (vWF) levels, and blood flow using venous occlusive plethysmography. After a 10-week treatment with enalapril or eprosartan, the sitting blood pressure in both the enalapril group (from 152.2 +/- 18.7 mmHg to 141.9 +/- 23.5 mmHg, P < 0.05) and eprosartan group (from 151 +/- 10.0 mmHg to 142.3 +/- 12.9 mmHg, P < 0.05) was significantly reduced. Significant diastolic blood pressure (DPB) reduction (from 94 +/- 8.7 to 84.5 +/- 9.6 mmHg, P < 0.05) and a greater DBP reduction response were found in the eprosartan group (63% in eprosartan versus 25% in enalapril). Additionally, dose-dependent reductions in the indices of platelet activation and endothelial dysfunction were observed in patients administered high dose treatments of eprosartan and enalapril, and the beneficial effects of these agents were not correlated with the reduction of blood pressure using both agents. Eprosartan is effective and well-tolerated in the treatment of mid-to-moderate hypertension, and the DBP response reduction to eprosartin was better than that to enalapril. A high dose of either eprosartan or enalapril significantly decreased the indices of platelet activation and endothelial dysfunction in hypertensive patients. The benefits of both agents cannot be explained solely by their antihypertensive effects and possibly may be mediated through their unique effect on angiotensin blockade.
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PMID:A double blind randomized trial to compare the effects of eprosartan and enalapril on blood pressure, platelets, and endothelium function in patients with essential hypertension. 1535 73

Endothelial damage and platelet hyperactivity may play a role in the vascular complications of essential hypertension. Restoration of endothelial function and reduction of increased platelet aggregation in essential hypertension are one of the aims of modern anti-hypertensive therapy. Therefore, the effect of angiotensin converting enzyme (ACE) inhibitors on endothelial and platelet functions is of interest. In the present study, 23 healthy normotensives and 23 age- and sex-matched patients with non-treated essential hypertension (1st and 2nd stage according to WHO) were investigated. Measurements of endothelial and platelet functions in hypertensives were carried out before therapy, after 1 week of placebo administration, after 1 week and after 1 month of perindopril therapy in a once daily dose of 4 mg. Plasma thrombomodulin (ELISA method) and beta-thromboglobulin (radio immunoassay method) were assayed and platelet aggregation (spontaneous and induced by adrenaline) was measured. The values of plasma thrombomodulin, a novel marker of endothelial function, were compared between age- and sex-matched normotensives and hypertensives. A significant decrease of adrenaline-induced platelet aggregation was observed after 1 month of perindopril therapy in comparison with the values before therapy or after 1 week of perindopril therapy ( P < 0.02 and P < 0.05 respectively). There were no significant changes in plasma thrombomodulin or beta-thromboglobulin following therapy. We failed to find significant changes of plasma thrombomodulin in patients in the early stages of hypertension, but its tendency to be higher than in normotensives does not rule out some vascular damage. The inhibitory effect of perindopril on platelet aggregation may be a further advantage of this drug. Since no changes were found after 1 week of therapy, the reduction of adrenaline-induced platelet aggregation after 1 month of therapy may be explained by an indirect effect of perindopril on platelet function, probably asa result of protective action on the arterial wall.
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PMID:Effects of the angiotensin-converting enzyme (ACE) inhibitor perindopril on endothelial and platelet functions in essential hypertension. 1679 47

Translational research (TR) can be defined as research where a discovery made in the laboratory (bench) can be applied in the diagnosis, treatment or prevention of a disease. Examples of medical discoveries contributing to translational medicine (TM) include the isolation of insulin by Banting (Nobel Laureate, 1923), the discovery of penicillin by Alexander Fleming (Nobel Laureate, 1945) and recently the discovery of the role of bacterium Helicobacter pylori in the causation of gastritis and peptic ulcer by Marshall and Warren (Nobel Laureates, 2005). Clinical research (CR) would be a more appropriate term for the bulk of research work undertaken by doctors. CR embraces both clinical based and laboratory-based research. The terminology "bedside to bench" applies more to CR as opposed to "bench to bedside" in the case of TR. But regardless of who does it, as long as the discovery can be translated to the bedside and results in improvement in patient care it can be considered a contribution to TM. Our work spans a 30-year period, involving laboratory-based research, clinical trials and genomics of IgA nephritis (Nx). This is a series of work to elucidate the pathogensis and therapy of IgANx. Plasma beta-thromboglobulin (BTG) an in-vivo index of platelet aggregation and anti-thrombin III increase due to a constant thrombogenecity resulting from platelet degranulation formed the basis for anti-platelet and low-dose warfarin therapy. A study of the natural history of IgANx revealed 2 courses, a slowly progressive course with end-stage renal failure (ESRF) at 7.7 years and a more rapid course at 3.3 years. Triple therapy (cyclophosphamide, persantin and low-dose warfarin) delayed progression to ESRF by about 8 years and for some patients up to 20 years. Documentation of abnormal suppressor T cell function provided the basis for immune therapy. Four patterns of proteinuria were present in IgANx and it is the quality and not so much the quantity of proteinuria which determined the prognosis. Low molecular weight proteinuria was a bad prognostic marker. A controlled therapeutic trial using ACEI/ATRA showed that therapy decreases proteinuria, improves renal function and converts non-selective to selective proteinuria. Subsequent work confirmed that it was the ATRA, not the ACEI which contributed to improved renal function. Individual anti proteinuria response to ATRA varies depending on ACE gene polymorphism. We found that the II genotype of the ACE gene was renoprotective and patients with this genotype had significantly reduced incidence of ESRF compared to those with the DD genotype. Patients responsive to ATRA therapy can retard progression to ESRF by up to 32 years. Mild renal failure can be reversed with possible regression of glomerulosclerosis because of glomerular remodelling by ATRA.
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PMID:3rd College of Physicians' lecture--translational research: From bench to bedside and from bedside to bench; incorporating a clinical research journey in IgA nephritis (1976 to 2006). 1710

Platelet aggregation using a single platelet counting technique in whole blood, was determined on 18 patients with primary Raynaud's phenomenon and 17 age-matched controls. Platelet aggregation in the Raynaud's patients was also assessed during a double-blind, crossover trial to investigate the efficacy of the angiotensin converting enzyme (ACE) inhibitor, enalapril. There were no differences in platelet aggregation to collagen, arachidonic acid, ADP or PAF, or in plasma levels of beta-thromboglobulin (BTG), platelet factor 4 (PF4) or thromboxane B(2) (TxB(2)) between the Raynaud's group and the normal controls. Similarly, there were no differences in these parameters in the Raynaud's group during treatment with enalapril when compared to placebo. It is concluded that patients with primary Raynaud's phenomenon have no evidence of abnormal platelet aggregation or increased platelet activation, and that platelet aggregation is not affected by enalapril.
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PMID:Platelet Aggregation in Primary Raynaud's Phenomenon and the Effect of Enalapril Administration. 2104 82