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

We present the core information from the "Reappraisal of European Guidelines on Hypertension Management", an official document of the European Society of Hypertension updating the current guidelines of 2007 based on the new knowledge that became available over the last two years. The division of antihypertensive agents into 5 main groups remains unchanged. The key discussion is about whether the treatment of hypertension in high-risk patients should be initiated already at high normal blood pressure and whether the target value should be 130 mm Hg and less. Both objectives are just speculative at present as they have not been confirmed in a large clinical study. Thanks to the HWET study we have more evidence for the benefits of hypertension therapy in older patients. Substantial part of the document focuses on combination therapy; the most encouraged combination is an ACE inhibitor + Ca blocker, or, alternatively, an ACE inhibitor or AII antagonist + diuretic. The beta-blocker + diuretic and ACE inhibitor + AII antagonist combinations are not recommended. Statins should be included in the therapy of all patients with hypertension, antiaggregation as a secondary prevention.
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PMID:[Reappraisal of guidelines on hypertension management]. 2032 88

In order to elucidate the involvement of the brain renin-angiotensin system (RAS) in cadmium intracerebroventricular (ICV) hypertension, we evaluated the effects of a pretreatment with different drugs: clonidine, an alpha(2) adrenergic agonist, enalapril and captopril, both ACE inhibitors, and saralasin, a competitive nonselective AT(1) and AT(2) receptor antagonist. We used a rat strain with low levels of kallikrein (LKR) that was more sensitive to ICV cadmium hypertension, compared with normal kallikrein rats (NKRs), the control strain. The interplay between the kallikrein-kinin system and the RAS in the LKR strain caused various hemodynamic alterations, which we believe were the result of elevated RAS activity in these animals. Moreover, we suggest that the defective kallikrein-kinin system in LKR may also cause an alteration in the activation of brain RAS in these animals. The LKR displayed elevated concentrations of plasma AII, hypertrophy of the myocardium, and initial alterations in the renal glomerulotubular system. With the exception of clonidine, all of the other drugs showed greater antihypertensive effects of differing statistical significance in LKR, compared with NKR. Both ACE inhibitors were able to significantly reduce pressor response to cadmium ICV in LKR throughout the experiment, whereas in NKR, they were only able to reduce the hypertensive peak of cadmium. A significant protective effect was also observed in LKR pretreated with saralasin, while no effect was observed in NKR. These findings confirm the presence of brain RAS activation in LKR and its contribution to the central control of pressor response to cadmium ICV.
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PMID:Brain renin-angiotensin system modifies the blood pressure response to intracerebroventricular cadmium in rats. 2042 3

In a series of papers in the Lancet and Lancet Neurology, comprising 3 post-hoc studies and one meta-analysis of hypertension and TIA trials, Peter Rothwell and coworkers showed that the within-person visit-to-visit blood pressure variability - changes in office blood pressure between visits spaced 3 months apart - is a strong risk predictor for stroke and coronary events. There was also a strong association between the so defined blood pressure variability and the classes of antihypertensive drugs that were used: beta-blockers and then diuretics increased variability most and reduced stroke risk least, calcium-antagonists increased variability least and reduced stroke risk most, in spite of comparable effects on mean blood pressure. ACE- inhibitors and AII receptor-antagonists had intermediate positions. The 'Rothwell' variability seems to be driven by different mechanisms than the short-term variability in blood pressure: it is likely that individual pharmacokinetic and dynamic properties drive the former, and that vessel wall characteristics and autonomic function drive the latter. Rothwell et al. do not argue the importance of mean or usual blood pressure as the most important risk predictor, but make a strong case for looking at the visit-to-visit blood pressure as well. In practice these findings most easily translate in to choosing drugs that provide stable blood pressures over time, such as calcium-antagonists for the elderly patients that took part in the Rothwell analyses.
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PMID:[High prognostic significance of blood pressure variability in consecutive checks]. 2097 7

Angiotensin-converting enzyme (ACE) is a dipeptidyl carboxypeptidase (EC 3.4.15.1) whose physiologic action is the conversion of AI to AII, and as such, it plays an important role in the regulation of blood pressure and fluid balance. ACE has been localized to endothelial cells throughout the body and epithelial cells in gut and kidney. It exists both as a membrane-bound enzyme and in a freely soluble form in plasma. The importance of the membrane-bound form is underscored by the recently described local renin-angiotensin system (RAS) in various organs, including heart, blood vessels, and kidney (1). In the heart and vascular smooth muscle, the local RAS is believed to play an important role in hypertrophy and remodeling. Accordingly, accurate and reliable methods for measurement of tissue (i.e., membrane bound) ACE activity are important, as well as soluble ACE activity.
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PMID:Quantification of Angiotensin-Converting Enzyme (ACE) Activity. 2133 22


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