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)

In the modern therapeutic approach to hypertension, the aspect of "metabolic side effects" is receiving ever more attention. This is the result of the recognition that high blood pressure forms part of a metabolic syndrome known as syndrome X, the components of which are variously influenced by different antihypertensive agents. Of particular importance seems to be the response of an underlying insulin resistance, since resulting hyperinsulinemia has been shown to be a separate risk factor. Negative metabolic influences on this syndrome may be a reason for inadequate prevention of coronary heart disease, as has been observed under conventional treatment despite effective lowering of blood pressure over many years. The spectrum of relevant antihypertensive drugs contains only few "metabolically neutral" or "metabolically positive" classes of substances, so that particular importance must be attached to ACE-inhibitors for use in patients with a "metabolic risk"; the most thoroughly studied of such inhibitors is captopril. In order to increase the responder rate to about 90%, a combination with low-dose hydrochlorothiazide can be recommended; the negative effect of the thiazide on insulin sensitivity is balanced by the positive effects of captopril. The great practicability of the single dose form of administration, the synergism of the individual substances, and "metabolic neutrality", together with the high level of tolerability underscore the advantage of this combination treatment.
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PMID:[Treatment of hypertension with consideration of metabolism. A challenge for current therapy of essential hypertension]. 851 26

Base on their own experience with isradipine and results of a multicentric study with amplodipine in the Slovak Republic, as well as based on data in the literature the authors conclude that: 1. In the treatment of arterial hypertension associated in the syndrome of insulin resistance (syndrome X and 5H resp.) with type 2 diabetes, hyperlipiproteinaemia and hyperinsulinism drugs of first choice include ACE-inhibitors and Ca antagonist of the second generation, dihydropiridine type, such as amplodipine, isradipine, fellodipine, nirtendipine etc. ACE inhibitors and Ca antagonist of the dihydropyridine type with prolonged effect have a good tolerance, few undesirable effect, a favourable effect on the decline of BP, regression of hypertrophy of the left ventricle and vascular wall; they do not cause deterioration of insulin resistance and thus do not interfere with compensation of diabetes and associated hyperlipoproteinaemia. 2. ACE inhibitors moreover reduce glomerular filtration and albuminuria and thus retard along with the effect on BP the progression of diabetic nephropathy. 3. In pre-existing hyporeninemic hypoaldosteronism (cca in 18% diabetic subjects) they can however cause dangerous hyperkalinaemia by further inhibition of the damaged renin-angiotensin-aldosterone system. In instances Ca inhibitors are indicated. The latter activate RAAS and do not have an impact on albuminuria. By their effect on the vas deferens they can increase glomerular filtration. 4. Diuretics are not suitable for the treatment of hypertension in X syndrome and the use of beta-blocking agents even with ISA and beta-1-selective preparations in restricted in particular when insulin is administered or other numerous contraindications are present (cardiac failure, bradyarrythmias, bronchitis etc.). Perhaps a combination of ACE-inhibitors and Ca antagonists of the 2nd generation with an alpha-blocking agent or hybrid alpha-beta-blocking agent is a suitable solution.
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PMID:[The role of calcium inhibitors in the treatment of arterial hypertension]. 924 72

Type II diabetes and hypertension are two pathologies which are frequently associated in adults, especially in developed countries. All the more so when patients are also obese: obesity is today, and will be in the next future, a true epidemic in these countries. These three pathologies imply a risk for cardiovascular complications much higher than that due to an isolated arterial hypertension. This increased risk is probably due to many factors: hyperglycemia, a dismetabolic syndrome (hyperlipemia, hyperuricemia, thrombophilia, altered Na(+)-H+ membrane exchanges = syndrome X) and hyperinsulinemia which favor atherosclerosis and clinical events. Consequently non-pharmacological and aggressive pharmacological therapy is necessary. Even if the trials done in the last years are questionable and not totally convincing, all researchers agree that lowering blood pressure to normality is the best way to improve prognosis of these patients. Usually for this purpose we need a therapy with more than one drug. Among the antihypertensive drugs, ACE-inhibitors (and perhaps also angiotensin receptor blockers) are preferred, especially in those hypertensives with diabetes who have also microalbuminuria or a frank proteinuria.
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PMID:[Diabetes and arterial hypertension]. 1177 8

Evidence links the insulin resistance syndrome with endothelial dysfunction. Previously, we have described a decreased endothelial nitric oxide synthase (eNOS) activity in both aortic endothelium and cardiac tissue, and an increased proliferation of aortic primary cultured vascular smooth muscle cells (pC-VSMCs), obtained from fructose-fed rats (FFR), an experimental model of syndrome X. Because the participation of the renin-angiotensin system (RAS) in this model is still unclear, the present study examined the effect of chronic administration of an angiotensin converting enzyme (ACE) inhibitor enalapril (E) on pC-VSMCs proliferation and eNOS activity in a conduit artery (aorta) and in resistance vessels (mesenteric vascular bed) from fructose-fed rats. Male Wistar rats were used: Control, FFR, Control + E, and FFR + E (n = 8 in each group). After 8 weeks, tissue samples were obtained and 10% fetal calf serum (FCS) proliferative effect was examined in pC-SMCs of aortic and mesenteric arteries by [(3)H]thymidine incorporation. The eNOS activity was estimated in endothelial lining from both origins by conversion of [(3)H]arginine into [(3)H]citrulline. The FFR aortic and mesenteric pC-VSMCs showed a significantly increased 10% FCS-induced [(3)H]thymidine incorporation compared to controls. The FFR aortic and mesenteric endothelium eNOS activity was significantly decreased. Chronic treatment with E abolished the increased proliferation and restored eNOS activity. These data confirm that changes in VSMCs proliferation and endothelial dysfunction at different levels of the vascular system are involved in syndrome X, and that the inhibition of angiotensin II production can revert those changes, suggesting an important role for RAS and possibly kinins, in the physiopathologic mechanism of this model of syndrome X.
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PMID:Effects of enalapril on the vascular wall in an experimental model of syndrome X. 1237 74

Centrally acting imidazoline I(1)-receptor agonists such as moxonidine and rilmenidine induce peripheral sympathoinhibition via the stimulation of hypothetical I(1)-receptors in the rostral ventrolateral medulla. Because of a rather weak affinity for alpha(2)-adrenoceptors, the use of these agents is associated with a lower incidence of adverse reactions, such as sedation and dry mouth, compared with classic centrally acting alpha(2)-adrenoceptor agonists (clonidine, guanfacine, methyldopa). The antihypertensive efficacy of moxonidine and rilmenidine is well documented, and they display a favorable hemodynamic profile. Their tolerability is better than that of the aforementioned centrally acting antihypertensive agents. However, long-term outcome data for moxonidine and rilmenidine are not available, and neither is a quantitative evaluation of their adverse effects. There exists some uncertainty with respect to the identity of the imidazoline I(1)-receptor, which has so far not been cloned. Furthermore, it would be desirable to develop highly selective I(1)-receptor agonists as successor drugs to moxonidine and rilmenidine. Although available data indicate that I(1)-receptor agonists are effective in patients with hypertension, comparative data versus agents such as beta-blockers, diuretics, calcium channel antagonists and ACE inhibitors are required to establish their position in the treatment of hypertension. Finally, I(1)-receptor agonists have potential in the treatment of patients with CHF and those with the metabolic syndrome; syndrome X.
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PMID:Centrally acting imidazoline I1-receptor agonists: do they have a place in the management of hypertension? 1472 14

Cardiological syndrome X (CSX) is defined as effort anginal pain, positive exercise tolerance test and absence of angiographically documented stenosis in coronary arteries. Some genetic predispositions and metabolic disturbances can participate in development of this syndrome. The aim of our study was to investigate the associations between some biochemical parameters and polymorphism of ACE and eNOS (VNTR and Glu298Asp) genes in patients with CSX. 36 patients with CSX and a control group of 30 healthy volunteers were included in the study. The genotypes were determined by the polymerase chain reaction. Our study revealed that patients with CSX exerted lower fasting NOx levels, tended to have higher insulin values measured at 1 h of oral glucose tolerance test and higher levels of triglycerides and free fatty acids during oral lipid tolerance test. Patients with genotype T/T Glu298Asp of eNOS and 4/4 VNTR of eNOS revealed lower levels of NOx compared to patients with genotypes G/G and 5/5, respectively (30.5 +/- 7.2 vs 13.2 +/- 4.5; 28.6 +/- 8.4 vs 14.2 +/- 7.4; p<0.05). Thus, we conclude that disturbances in free fatty acid utilization, estimated by postprandial lipaemic test play important roles in the development of endothelial injury in CSX.
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PMID:[Relations between endothelial nitric oxide synthase and angiotensin-converting gene polymorphisms and certain biochemical parameters in patients with cardiac syndrome X]. 1572 77

Atherothrombosis has long been recognized as an important mechanism of cardiac events in ischemic heart disease, and large multicenter clinical studies have shown the benefit of antiplatelet agents, statins, beta-blockers and angiotensin converting enzyme inhibitors in preventing these events. However, more recent studies have been less successful at showing incremental gains in targeting these mechanisms, suggesting that the limits of this strategy have been exploited. Coronary vasoconstriction is another important mechanism in ischemic heart disease but has received little attention and yet is a potential therapeutic target. In the current review, the reasons why coronary vasconstriction has received insufficient consideration are explored. In particular, we need to change our approach from lumping heterogeneous clinical entities together to focusing on clinically-discrete homogeneous groups with a common mechanism and thus therapeutic target. The role of coronary vasoconstriction is examined in the various ischemic syndromes (variant angina, chronic stable angina, acute coronary syndromes and syndrome X) and the underlying mechanisms discussed. Finally, in order to advance studies in this field, an innovative research strategy is proposed, including: (1) selection of paradigmatic cases for the various ischemic syndromes; (2) candidate therapeutic targets; and (3) approaches in assessing the clinical efficacy of these potential therapies.
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PMID:Role of coronary vasoconstriction in ischemic heart disease and search for novel therapeutic targets. 1920 3

Aim of this study was to investigate the possible relationship between ACE and/or PON1 M55L, Q192R genetic polymorphisms and subjects with Coronary Heart Disease (CHD) and/or syndrome X (SX) when compared to the control group. ACE I/D, PON1 M55L and Q192R genetic polymorphisms, Body Mass Index (BMI) and biochemical parameters were investigated in subjects with CHD (n = 19), SX (n = 34) and healthy subjects (n = 26). All of the subjects were nonsmokers. According to the unrelated group t-test results; BMI, HDL-C and TG values were found to be slightly different in SX and control subjects but there was no significant difference in LDL-C and TC values. According to the Mann Whitney U-test results, BMI, TC, HDL-C and LDL-C values were found to be significantly different among CHD and control group subjects, but there was no difference in TG values. The results of this study indicates that ACE, PON1 192 and PON1 55 gene polymorphisms are not related to genetic susceptibility to SX and/or CHD in non-smokers. Obviously, the interpretation of these finding is difficult due to the small sample size and larger group studies are needed for more definitive conclusions.
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PMID:Role of angiotensin converting enzyme, paraoxonase 1 55, 192 gene polymorphisms in syndrome X and coronary heart disease. 1957 17

Cardiac syndrome X (CSX) is defined as a typical anginal-like chest pain with a transient ischemic electrocardiogram, but without abnormal coronary angiography. It is usually accepted that endothelial dysfunction, inflammation, oxidative stress and estrogen deficiency are the main reasons of CSX. There are some methods to treat CSX including statins, b blocker, angiotensin converting enzyme inhibitors, nitrates, estrogen, and so on. The estrogen replacement therapy (ERT), in particular, has been reported by many researchers to significantly reduce the frequency of chest pain after administration of estrogen, which has been explained as estrogen acting on its receptor to improve the endothelial function. However, it has been suggested that ERT must not be used for coronary heart disease due to its adverse effects. However, some selective estrogen receptor modulators (SERMs) can inhibit inflammatory response as well as oxidative stress, and improve the endothelial function, to reduce the occurrence of chest pain. Here, we hypothesize that SERMs may be the beneficial selection for patients with CSX.
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PMID:Selective estrogen receptor modulators promising for cardiac syndrome X. 2093 11

Angina in the absence of obstructive coronary artery disease, sometimes referred to as cardiac syndrome X (CSX), is a debilitating condition that disproportionately affects women. More than 50% of women evaluated for angina have non-obstructive disease by cardiac catheterization, although the total numbers of women affected by CSX are unknown. Varying clinical definitions and the lack of large scale epidemiologic studies focusing on this illness have resulted in limited knowledge about its risk factors, although there appears to be an association with black race, estrogen deficiency, and insulin resistance. Contrary to prior beliefs about the benign nature of this entity, these women suffer considerable morbidity with costly economic implications that approach the lifetime costs of healthcare utilization for those with obstructive coronary disease. Two prevailing hypotheses have emerged to explain CSX: the ischemic hypothesis detailing abnormal coronary microvascular function and the non-ischemic hypothesis describing altered pain perception and myocardial hypersensitivity. Treatment strategies have focused on both of these pathways with the main goal of improving symptoms. Beta blockers provide the most convincing evidence for benefit, with other antianginals having secondary roles. Other promising pharmacologic therapies include xanthine derivatives, estrogen replacement therapy, ACE inhibitors, and statin medications, among other emerging treatment options. Neurostimulation and lifestyle factors including exercise can also be beneficial in reducing symptoms. However, managing patients with CSX can be frustrating for both patients and physicians, as there is a lack of data regarding an optimal treatment algorithm including few large-scale randomized controlled trials to clarify effective therapies.
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PMID:Angina in Women without Obstructive Coronary Artery Disease. 2128 81


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