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)

By means of high voltage electrophoresis experiments it could be demonstrated that the dipeptide hydrolase present in the plasma of Bothrops jararaca is similar to the angiotensin I converting enzyme of human plasma. Therefore, angiotensin I can be considered as a probable natural substrate for this potent snake peptidase in contrast to bradykinin, which is excluded in that case, since this snake plasma was previously found to be deficient in intrinsic kinin releasing system. On the other hand, the presence of angiotensinase activity in this snake plasma could also be demonstrated. Through the pharmacological comparison of angiotensin II with the pressor peptide released from the Bothrops jararaca plasma by chymotrypsin, an indirect indication of the presence of angiotensinogen in the plasma of this reptile was obtained.
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PMID:Components of the renin-angiotensin system in the plasma of Bothrops jararaca. 20 19

ACE-inhibitors improve symptoms and prognosis in patients with heart failure. The V-Heft II trial has demonstrated that the beneficial effect of these agents is superior to unspecific vasodilators. Besides sustained arterial and venous vasodilation the inhibition of the neurohumoral axis is thought to play an important role. Angiotensin II and catecholamines not only exert vasoconstrictor effects, but might also contribute to vascular and myocardial growth. Thus, it may not be surprising that the beneficial effects of ACE inhibitors in heart failure only emerge during long-term therapy rather than after short-term administration. It has been shown that these agents improve blood flow to skeletal muscle during exercise after chronic therapy (not acutely), and there is some preliminary evidence that improvement of endothelial function might be involved in this effect, i.e., by reducing the degradation of bradykinin, an endothelial vasodilator. ACE inhibitors reduce LV hypertrophy, an important risk factor for cardiovascular disease and prognosis. Moreover, there is experimental evidence that ACE inhibitors can prevent and even reverse interstitial fibrosis in the left ventricle. Although the plasma renin activity may be normal in patients with chronic heart failure, recent data using polymerase chain reaction indicate that the tissue cardiac renin angiotensin system is activated in the failing human heart as assessed by measurements of angiotensin converting enzyme mRNA and angiotensinogen mRNA which may be an important target for ACE-inhibition.
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PMID:[The value of ACE inhibitors in heart failure (mechanism of action)]. 129 Mar 8

To investigate the possible role of vascular angiotensin converting enzyme (ACE) in the development and maintenance of hypertension, we examined aortic ACE messenger RNA (mRNA) levels in two-kidney, one clip (2K1C) hypertensive rats. The blood pressure was increased remarkably at 4 weeks (early stage) after clipping and remained elevated at 12 weeks (chronic stage). The aorta ACE mRNA levels were significantly elevated in both early and chronic stages concurrently with the increases in aortic ACE activity and blood pressure. The plasma renin activity rose markedly at 4 weeks, but returned to the normal level at 12 weeks. Neither ACE activity in the lung and plasma, nor ACE mRNA level in the lung was altered at either stage. The aorta and liver angiotensinogen mRNA levels and renal renin mRNA level were increased at 4 weeks but decreased at 12 weeks. These results indicate that the acceleration of all components in the renin-angiotensin system may contribute to the development of 2K1C hypertension in the early stage. In the chronic stage, the increased vascular ACE induced by the elevated ACE mRNA levels in the aorta may play the primary role in the acceleration of local angiotensin II formation and thus may sustain the hypertension.
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PMID:Increase of angiotensin converting enzyme gene expression in the hypertensive aorta. 132 65

Myocardial hypertrophy in response to hemodynamic overload is an established risk factor for cardiovascular morbidity and mortality. Partially, this may be due to alterations in cardiac gene expression, resulting in a more fetal-like myocyte phenotype with a fragile Ca(++)-homeostasis. Depressed expression of the sarcoplasmic reticulum Ca(++)-ATPase is the hallmark of this overload phenotype, contributing to prolonged cytosolic Ca(++)-transients, disturbed diastolic relaxation, altered force-frequency relation, and probably, electrophysiologic instability with susceptibility to malignant arrhythmias. Since angiotensin II is a growth-promoting factor in several cellular systems, the local formation of angiotensin II within the myocardium might contribute to the trophic response and the phenotype shift of overloaded myocardium. Several observations are consistent with this hypothesis: the cardiac expression of ACE and angiotensinogen is enhanced in experimental myocardial overload and in human endstage congestive heart failure; prolonged observations of experimental cardiac overload with hypertrophy-induced putative normalisation of myocardial systolic wall stress demonstrated a renormalization of ventricular tissue ACE activity and of ventricular sarcoplasmic Ca(++)-ATPase expression and activity; normalizing ventricular tissue ACE activity in experimental cardiac overload by chronic nonhypotensive ACE inhibitor therapy caused a parallel partial normalization of hypertrophy and underexpression of sarcoplasmic CA(++)-ATPase. This partial normalization of myocyte Ca(++)-homeostasis in overload hypertrophy by non-hypotensive chronic ACE-inhibition is attenuated by concomitant chronic application of bradykinin-2 receptor blockade, indicating an involvement of altered bradykinin metabolism in the phenotype modulation due to chronic ACE inhibition. While these observations are consistent with a direct influence of local ACE activity on the sarcoplasmic reticulum, the cell type contributing to the enhanced ACE expression in overload and the specific mechanism of this influence are unknown.
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PMID:Modulation of myocardial sarcoplasmic reticulum Ca(++)-ATPase in cardiac hypertrophy by angiotensin converting enzyme? 133 65

This report summarizes the present data about the existence of components of the renin-angiotensin system in the rat brain. Angiotensinogen mRNA, mas proto-oncogene mRNA, angiotensin II (Ang II), and Ang II receptors have been mapped in the brain by using in situ hybridization, immunocytochemistry, and receptor autoradiography. These markers turned out to be widely distributed throughout the brain and to be not only restricted to areas related to cardiovascular control, but also to be present in functionally different areas, suggesting also other functions of angiotensin peptides. The distribution patterns of these components were correlated with data on the distribution of angiotensinogen, renin, angiotensin converting enzyme, and angiotensin fragments that revealed substantial topological mismatches. Using the model of "volume transmission," possible explanations for these mismatches are proposed. In this regard, a possible involvement of angiotensin fragments and the mas proto-oncogene in the functioning of the brain renin-angiotensin system is also discussed, demonstrating the increasing complexity of this central regulatory system.
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PMID:The brain renin-angiotensin system: localization and general significance. 138 66

Angiotensinogen is the precursor molecule of one of the most potent vasoactive substances, angiotensin-II. Angiotensinogen is normally synthesized in the liver and secreted into the plasma where it is converted into angiotensin-II by the combined proteolytic action of renin and angiotensin converting enzyme. Angiotensinogen levels in the plasma are modulated by a number of pathological and physiological factors. In order to understand the regulation of angiotensinogen gene expression, we have constructed an expression vector in which 688 bp of the 5'-flanking region of the rat angiotensinogen gene were attached to the chloramphenicol acetyl transferase (CAT) coding sequence. We have also obtained 5'-sequential deletion mutants from the rat angiotensinogen promoter attached to the CAT gene, and have identified multiple cis-acting DNA sequences involved in the regulation of angiotensinogen gene expression by transient transfection of these recombinant DNA molecules in human hepatoma cell lines, Hep3B, and HepG2.
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PMID:Identification of cis-acting DNA elements involved in the regulation of angiotensinogen gene expression. 155 46

Increasing evidence points toward local production of renin and angiotensinogen in the artery wall. Because angiotensin converting enzyme (ACE) inhibitors have been shown to block intimal hyperplasia after arterial injury in the rat, it has been suggested that angiotensin II is an important mediator of the proliferative response to vascular injury. To prove that previous observations with use of ACE inhibitors are a result of effects on local angiotensin levels versus nonspecific drug effects, we tested the ability of an unrelated drug, the angiotensin II receptor antagonist saralasin, to similarly block intimal hyperplasia after aortic injury in the rat. Balloon catheter aortic denudation was performed in 28 rats pharmacologically treated for 14 days after surgery and split into four groups: group 1, saralasin 360 micrograms/kg/hr intravenously; group two, normal saline 0.5 mm3/hr intravenously; group 3, captopril 100 mg/kg/day orally; and group 4, heparin 50 U/kg/hr intravenously. Animals were killed and aortas were perfusion fixed at physiologic pressure 14 days after denudation. Cross-sectional intima-to-media ratios were calculated by computerized planimetry. Compared with saline controls, saralasin inhibited intimal hyperplasia 45% (p less than 0.001), captopril 59% (p less than 0.001), and heparin 68% (p less than 0.001). A reduction in total intimal area was also evident in animals treated with saralasin (p less than 0.01). Blood pressure in the group treated with captopril decreased from 107.4 +/- 3.9 to 96.3 +/- 4.3 mm Hg (p less than 0.01) after 6 days, whereas saralasin and heparin had no effect on blood pressure. Weight gain during the study was reduced in groups treated with captopril and heparin but not in the group treated with saralasin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of injury induced intimal hyperplasia by saralasin in rats. 156 May 60

The local renin-angiotensin system may regulate adrenal cell growth and function. Angiotensinogen, renin, and angiotensin converting enzyme gene expression were studied in four normal adrenal glands (removed from patients with renal carcinomas) and five aldosterone-secreting adenomas. Northern blot analysis showed expression of angiotensinogen messenger RNA (mRNA) in normal adrenals at levels approximately 35-fold lower than liver and sixfold lower than kidney. Similar angiotensinogen mRNA levels were present in two aldosteronomas, whereas a third had levels approximately 50% of those found in kidney. Renin mRNA was detectable in most normal adrenals and in three adenomas, one of which had relatively high renin mRNA levels. Angiotensin converting enzyme gene was expressed in adrenal tissue and in three adenomas. Portions from these normal adrenals and two of these aldosteronomas, as well as samples from two other adrenals and three aldosteronomas, were also studied in an in vitro superfusion system coupled with active renin radioimmunometric assay, angiotensin II/III, and aldosterone radioimmunoassay. Total amounts of active renin and angiotensin II/III released from normal adrenals during 270 minutes of superfusion were higher than the amounts released from aldosteronomas (312 +/- 35 versus 187 +/- 43 and 823 +/- 100 versus 436 +/- 55 pg/100 mg tissue, respectively; mean +/- SEM, p less than 0.05), whereas aldosterone release from the adenomatous tissue was approximately threefold higher (320 +/- 21 versus 115 +/- 18 ng/100 mg tissue; mean +/- SEM, p less than 0.01). Total amounts of active renin and angiotensin II/III released by normal or adenomatous adrenal samples exceeded threefold to fourfold the amounts extracted from similar samples of the same surgical specimen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Local renin-angiotensin system in human adrenals and aldosteronomas. 159 71

Protein meals and infusion of amino acids cause an increase of glomerular filtration rate in humans and animals with normal renal function despite the circulating renin concentration remaining unchanged. The renal hemodynamic response is not altered by angiotensin converting enzyme inhibitors, but it is obliterated by cyclooxygenase inhibitors. By contrast, chronic exposure to high protein diets raises circulating renin and increases messenger RNA of renin (but not of angiotensinogen) in kidney tissue. Chronically high protein intake raises the glomerular filtration rate and reduces glomerular permselectivity; the reverse is seen with low protein intake. In patients with renal failure, acute amino acid infusion or protein meals cause a paradoxical drop in glomerular filtration rate which is not influenced by converting enzyme inhibitors.
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PMID:Influence of dietary factors on the renal renin-angiotensin system. 161 90

Two enzymes with tonin-like activity, designated rSMT3 and rSMT4, were purified from rat submandibular glands and another, rPT1, was obtained from the prostate. The three enzyme fractions hydrolysed angiotensin I, angiotensinogen (AG) and synthetic AG(1-14) to form angiotensin II. With angiotensin I as substrate, pH optima were 6.5 for rSMT3, 6.8 for rSMT4 and 7.5 for rPT1. With AG(1-14), the three enzymes had optimal activity at pH 7.5. The three enzymes had negligible activity upon a kallikrein substrate, Ac-Phe-Arg-Nan. The enzymes were inhibited by aprotinin, soybean trypsin inhibitor and phenylmethanesulfonyl fluoride but not by two angiotensin converting enzyme inhibitors, ethylenediaminetetracetic acid or enalaprilat. N-tosyl-L-phenylalanine chloromethyl ketone (1 mM) inhibited rPT1 and rSMT4 but not rSMT3. Molecular weights (SDS-PAGE) were 31,700 for rSMT3, 29,800 for rSMT4 and 28,100 for rPT1. Total activity in the prostate is 150-times lower than in the submandibular gland, where 92% of the tonin activity is related to rSMT4. Physical and chemical properties suggest that rSMT4 is tonin, whereas rSMT3 and rPT1 are tonin-like enzymes which can generate angiotensin II from different substrates.
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PMID:Identification of serine proteinases with tonin-like activity in the rat submandibular and prostate glands. 164 31


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