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 relationship between experimental magnesium deficiency and blood pressure is complex and still the subject of much debate. The effect of Mg deficiency and blood pressure in Wistar rats receiving a Mg deficient diet (0.080 g/kg) for 40 weeks was examined. Deficient rats, when compared to controls, showed an initial transitory phase of hypotension, followed by normalization of blood pressure and then hypertension beginning after 15 weeks on the deficient diet. During the whole experimental period, heart rate was significantly increased in deficient rats as compared to controls. The fact that hypotension resulting from Mg deficiency of short duration can be inhibited by antihistamines and by indomethacin suggests that various mediators seen during the inflammatory period of Mg deficiency could be involved. Mg deficiency of long duration was accompanied by hypertension. When Mg-deficient rats received the control diet for a period of 3 weeks, Mg supplementation only partially corrected the hypertension. The hypertension was not a consequence of stimulation of the renin-angiotensin system since the plasma renin activity was not modified and ACE activity was reduced. These deficient rats showed a significantly lower vasopressor response to noradrenaline than control rats. Several factors such as increase in collagen, changes in elastin and arterial elasticity, total lipid content, and calcifications may account for the hyporesponsiveness to contractile agonists.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Magnesium and blood pressure. I. Animal studies. 139 7

Electrolyte abnormalities are a frequent and potentially hazardous complication in patients with heart failure. This may be due to the pathophysiological alterations seen in the heart failure state leading to neurohumoral activation (stimulation of the renin-angiotensin-aldosterone system, sympathoadrenergic stimulation), and due to the complications of therapy with diuretics, cardiac glycosides or ACE inhibitors. Patients with heart failure may exhibit hyponatremia due to a decrease in water excretion, which may be related to the enhanced release of both angiotensin and vasopressin and can be exaggerated by diuretic therapy. Along with potassium and calcium, magnesium influences cardiovascular function. Magnesium and potassium deficiencies play an important role in the development of cardiac arrhythmias. Magnesium is essential for the maintenance of intracellular potassium concentration. Although there are conflicting data regarding the prevalence of hypomagnesemia in patients with chronic heart failure (the values range from 7-37%), multiple studies have documented lower magnesium concentrations in patients with heart failure than in normal controls. As magnesium and potassium are mainly intracellular ions, measurements in serum or plasma are of limited value to assess magnesium status. There was no correlation between the intracellular electrolyte content and the electrolyte levels in plasma, either for mononuclear cells or erythrocytes or for myocardial and skeletal muscle. Loop diuretics (e.g. furosemide) are supposed to cause a substantial loss of both magnesium and potassium in the plasma and intracellular space. The potassium-sparing diuretics amiloride and triamterene are reported to also exert magnesium-sparing effects. Recently, ACE inhibitors have been documented to have important magnesium-conserving actions, possibly via their effect on glomerular filtration. Hyperkalemia, secondary to the use of ACE inhibitors in patients with heart failure, is well documented. Digoxin directly limits the renal tubular reabsorption of magnesium, therefore increasing magnesium excretion. Low magnesium and potassium concentrations increase cardiac glycoside toxicity. In contrast, elevated levels of magnesium decrease the sensitivity of human myocardium to antiarrhythmogenic actions of cardiac glycosides, without affecting maximally developed tension. Moreover, magnesium increases binding affinity of cardiac glycosides to the receptor. The antiarrhythmic action of magnesium is suspected to be mediated by a reduced sensitivity to electrophysiological changes induced by Ca2+, thus indicating Ca2+ antagonistic properties of magnesium. Magnesium deficiency has also been implicated in sudden death, notably in patients with congestive heart failure. Therefore, when treating congestive heart failure, one must consider how to prevent depletion of electrolytes or how to replete potassium and magnesium in deficiency states.
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PMID:Heart failure and electrolyte disturbances. 150 35

We have previously reported that antioxidant drug intervention protects against magnesium deficiency-induced myocardial lesions. In the present study, Golden Syrian male hamsters were fed either a magnesium-deficient diet or a magnesium-supplemented diet. Animals from each group received sulfhydryl-containing angiotensin converting enzyme inhibitors: captopril, epi-captopril (a stereoisomer of captopril), and zofenopril* (arginine blend of zofenopril containing a free SH group); another group of animals received the non-sulfhydryl-containing angiotensin converting enzyme inhibitor enalaprilat. The animals were killed after 14 days, and their hearts were isolated for morphological and morphometric analyses. Hematoxylin and eosin-stained sections were examined by a computer image analysis system for a morphometric determination of the severity of myocardial injury. Captopril reduced both the density of lesions, from 0.32 to 0.08 lesions/(mm2) (p less than 0.01), and the area fraction of lesions, from 7.42 x 10(-4) to 2.03 x 10(-4) lesion area/(mm2) (p less than 0.01), as well as the degree of inflammatory infiltration around the blood vessels. Epi-captopril and zofenopril* were virtually equipotent to captopril, but enalaprilat afforded only slight (nonsignificant) protection. These results indicate that a significant component of the protective effect of captopril in this model was attributable to its sulfhydryl moiety, rather than solely due to the inhibition of the angiotensin converting enzyme. These data further support our previous findings of possible free radical participation in cardiomyopathy due to magnesium deficiency.
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PMID:Captopril protects against myocardial injury induced by magnesium deficiency. 165 86

Bartter's syndrome (BS) is a disease with severe hypokalaemia due to renal potassium wasting. The potassium loss is due to lesions at different sites within the renale tubule. Additional features include metabolic alkalosis, excess renal production of prostaglandins, hyperreninaemia, hyperaldosteronism and impaired pressor responses to exogenous angiotensin II. These secondary features are the result of renal potassium wasting. Symptoms are due to potassium deficiency, but many adult patients feel well despite marked hypokalaemia. The hypocalciuric variant of BS is called Gitelman's syndrome. These patients have a more benign course. The diagnosis of BS is one of exclusion, mainly of surreptitious vomiting, diuretic or laxative abuse. The primary treatment is potassium supplementation often in combination with potassium-sparing diuretics, prostaglandin inhibitors or ACE-inhibitors. With coexisting magnesium deficiency, magnesium supplementation might be effective.
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PMID:[Bartter's syndrome. A condition with chronic hypokalemia]. 896 74

Dietary modification is an inefficient and calorically unwise means of preventing hypokalemia; potassium supplements present compliance problems and are of little or no use in the patient with a concomitant magnesium deficiency. Prescribing potassium-sparing diuretics is the best prevention-oriented choice, but diabetics and older patients must be monitored for signs of hyperkalemia, and it is generally better not to use these agents in patients who are also taking ACE inhibitors.
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PMID:Preventing hypokalemia 1153 14

The medical management of Marfan Syndrome (MFS) mainly relies on early prevention of the aortic complications. Hemodynamic treatments try to diminish the forcefulness of cardiac contractions and to reduce blood pressure: for example long term administration of propranolol may significantly reduce the rate of increase in aortic ratio (aortic diameter/expected aortic diameter). Retardation of aortic dilatation may be most often observed by early treatment started when the baseline end-diastolic aortic root diameter is < 40 mm. It seems better to use beta-blockers without intrinsic sympathomimetic activity. Successful acceptance of beta-blockers may be limited by side-effects, but the efficiency of alternative hypotensive agents (calcium channel inhibitors, ACE inhibitors) is not yet validated. Gene therapy might constitute an etiologic specific treatment of MFS. FBN1-RZ1 hammerhead antisense ribozyme is able to suppress expression of the mutant FBN1 allele. The use of ribozymes as systemic therapeutic agents will depend on efficient delivery to its target, but the various proposed vectors raise yet unsolved problems. A hydrogel angioplasty balloon might be a possible vector for delivering an antisense ribozyme in the aortic wall specifically. Ribozymes--as deoxyribonucleotides--may be taken up by tissue upon local application. Further research should study ex vivo local application of antisense ribozyme on human aortic wall, before assessing in vivo efficiency and tolerance of this aortic local vectorisation. It is always necessary to maintain a balanced magnesium intake in patients with MFS. Firstly to prevent the multiple noxious effects of magnesium deficiency on cardiovascular targets. Secondly to ensure the best efficiency and the least toxicity of the hemodynamic drugs used as long term prophylactic treatment for cardiovascular complications and of the etiologic antisense magnesium-dependent gene therapy, in the future.
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PMID:Marfan syndrome, magnesium status and medical prevention of cardiovascular complications by hemodynamic treatments and antisense gene therapy. 1273 84