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 liver of male ddY mice intoxicated once with carbon tetrachloride (CCl4), the change in lipid peroxide (LPO) level with the development of damage over a 24 hr period after i.p. treatment of the toxicant (1.0 mL/kg) was compared with the changes in reduced glutathione (GSH) and oxidized glutathione (GSSG) levels, GSSG/GSH ratio, and activities of the glutathione redox cycle-related enzymes such as Se-dependent glutathione peroxidase (Se-GSH-px), glutathione reductase (GSSG reductase), and glucose-6-phosphate dehydrogenase (G-6-PDH) and of Se-independent glutathione peroxidase (non-Se-GSH-px) with the development of damage during the same period. An apparent liver injury was observed 0.5 hr after CCl4 treatment and the injury progressed rapidly later than 8 hr, judging from the activities of serum transaminases, marker enzymes of liver cell damage. Hepatic LPO level slightly increased once during the first 4 hr after CCl4 treatment and a marked increase in the level occurred later than 12 h, while serum LPO level increased later than 12 h. Hepatic GSH level decreased rapidly during the first 4 hr after CCl4 treatment and the decreased level recovered slowly thereafter, although the recovered level did not reach the control level. Hepatic GSSG level rapidly increased once during the first 1 hr after CCl4 treatment and an increase in the level occurred again later than 12 h. Hepatic GSSG/GSH increased during the first 1 hr and later than 8 hr after CCl4 treatment, although the ratio was maintained above the control level later than 0.5 h. Hepatic Se-GSH-px activity increased during the first 2 hr after CCl4 treatment and later than 8 h, while hepatic non-Se-GSH-px activity increased during the first 1 hr but decreased below the control level at 8 and 12 h. Hepatic GSSG reductase activity decreased during the first 2 hr after CCl4 treatment but the decrease activity returned up to the control level at 8 h. Hepatic G-6-PDH activity increased rapidly during the first 2 hr after CCl4 treatment and the increase proceeded slowly thereafter. These results indicate that although hepatic lipid peroxidation is enhanced at early and progressed stages of liver injury in mice intoxicated once with CCl4, endogenous GSH through hepatic glutathione redox cycle can respond well to enhanced hepatic lipid peroxidation at an early stage of liver injury but not enough to enhanced hepatic lipid peroxidation at a progressed stage of liver injury.
Res Commun Mol Pathol Pharmacol 1996 Aug
PMID:Response of endogenous reduced glutathione through hepatic glutathione redox cycle to enhancement of hepatic lipid peroxidation with the development of acute liver injury in mice intoxicated with carbon tetrachloride. 888 91

An atheroma-like neo-intima was produced by positioning a flexible collar around the common carotid arteries of normocholesterolaemic rabbits. Vessel segments taken from the mid-region of the collared and control region of the same artery were studied 7 days after surgery. Placebo rabbits were provided ab libitum with regular tap water, and treated animals were supplied with water containing perindopril (0.3 mg/kg/day) for 14 days. Perindopril treatment reduced plasma angiotensin converting enzyme (ACE) activity by 88%, but did not significantly alter arterial blood pressure or heart rate. In control rings from placebo rabbits perindoprilat in vitro (0.1-1.0 microM) reduced the sensitivity to angiotension I up to 20-fold but did not affect that of angiotensin II. In placebo rabbits, the collared arterial segments were approximately five-fold more sensitive to the vasoconstrictor action of 5-HT (P < 0.05) than the corresponding control segments. Perindopril treatment did not prevent the supersensitivity of the collared vessels to 5-HT. Development of the lesion in placebo or perindopril-treated rabbits did not alter the vascular sensitivity to either angiotensin I (10(-9)-10(-5)M) or angiotensin II (10(-10)-10(-6)M). The vasorelaxant action of sodium nitroprusside was similar in collared and control rings, whereas the maximum endothelium-dependent vasorelaxant response to acetylcholine was reduced from 68 +/- 5% in control rings, to 44 +/- 8% (mean +/- S.E.M., n = 9, P < 0.05) in collared rings of placebo-treated rabbits. In the perindopril-treated animals, this impairment of relaxation was restored in collared vessels and was no longer significantly different from the control sections. In contrast, perindoprilat in vitro (1.0 microM) did not alter the vasorelaxant response to acetylcholine in control or collared rings in a separate series of placebo rabbits. Morphologically, vessel segments taken from the centre of the collared artery of all placebo rabbits showed a thickened intima filled with cells that had the appearance of synthetic-state smooth muscle. The intimal/medial cross-sectional area ratio was reduced from 0.11 +/- 0.02 (n = 10) in placebo rabbits to 0.05 +/- 0.01 (n = 9) in perindopril-treated rabbits, whereas cross-sectional area of media of the collared vessels was similar in the two groups. Thus ACE may have important roles in the initiation and progression of atheroma-like lesions. Inhibition of ACE with perindopril reduces intimal thickening and restores the defective vasodilatation induced by the endothelial-dependent vasodilator, acetylcholine.
J Mol Cell Cardiol 1996 Sep
PMID:Perindopril treatment prevents the loss of endothelial nitric oxide function and development of neo-intima in rabbits. 889 57

Chronic heart failure is a well-recognized syndrome in which left ventricular impairment produces a constellation of secondary changes in other organ symptoms leading to symptoms such as muscular fatigue and dyspnoea and objective limitation to exercise tolerance. With modern drug therapy of diuretics and ACE inhibitors, the majority of patients have minimal if any signs of congestion, and yet severe symptomatic limitation remains. This limitation bears little relationship to conventional measures of either left ventricular function or the haemodynamic profile of the patient. The symptoms limiting exercise are predominantly fatigue or dyspnoea, and yet the classical pathophysiological explanations for their genesis now seem inadequate. Recent investigations, as demonstrated, in part, by the research presented in this symposium, attest to the importance of abnormalities in peripheral blood flow and in skeletal muscle in producing both objective limitation to exercise and in explaining the generation of the exercise-limiting symptoms of the syndrome of stable optimally treated chronic heart failure. In addition it is now evident that these muscle changes may in addition have pathophysiological significance for the maintenance of sympatho-excitation during exercise and potentially therefore in the progression of left ventricular remodelling and in the susceptibility to ventricular arrhythmias. This paper presents some of the background evidence which leads to the hypothesis that a feedback loop links changes in skeletal muscle to abnormal reflex cardiopulmonary control which may both limit exercise and be harmful in the progression of the syndrome.
J Mol Cell Cardiol 1996 Nov
PMID:The "muscle hypothesis" of chronic heart failure. 893 79

Metabolic fates of pyruvate (CO2, lactate, citrate) in normal and neoplastic cells have been assessed. Pyruvate consumption by tumour cells falls (by 72-85%) and mean percentage oxidation rises from 75% to 91% with hydroxycitrate. Ratios of rates of oxidation of (3-(14)C-pyruvate) : (1-(14)C-pyruvate), indicating CO2 produced from TCA cycle activity : that from PDH activity, are higher for tumorigenic (0.17-0.24) than for non-tumorigenic (0.005-0.04) cells and increase (0.27-0.65 and 0.13-0.29, respectively) with hydroxycitrate. Although maximal ATP-citrate lyase activities do not correlate with malignancy, citrate may be a major fate of glutaminolytic pyruvate in tumour cells. Citrate accounts for 14-37% of consumed glutamine compared with 11-13% being recovered as CO2. By contrast, approximately 100% of glycolytic pyruvate is converted to lactate.
Biochem Mol Biol Int 1996 Nov
PMID:Hydroxycitrate causes altered pyruvate metabolism by tumorigenic cells. 895 95

Rapid growth of the left ventricle of the newborn pig heart can be restrained by treating piglets with the angiotensin converting enzyme inhibitor, enalapril maleate. This reduced rate of growth is reflected in vitro by reduced rates of ribosome formation and protein synthesis, and may be due to decreased availability of angiotensin II (AII), a potentially hypertrophic agent; decreased numbers of AII receptors; increased availability of bradykinin, a potentially antihypertrophic agent; or reduced hemodynamic load on the left ventricle. Because enalapril decreases degradation of bradykinin, the role of bradykinin as an inhibitor of cardiac growth in the newborn heart was investigated. Addition of 1 x 10(-5) M bradykinin and 1 x 10(-6) M enalapril to the perfusate of isolated hearts from 2 day old piglets did not significantly alter heart rate, contents of ATP or creatine phosphate or rates of ribosome formation or protein synthesis during 1 h of perfusion. Similarly, exposure of myocytes isolated from the left ventricular free wall of piglets to 5 x 10(-6) M bradykinin for 72 h did not alter the rate of [3H]-phenylalanine incorporation into total protein. The reduced rate of left ventricular growth in vivo caused by enalapril administration was not reversed by simultaneous treatment with the specific bradykinin receptor antagonist, HOE 140. HOE 140 alone did not alter ventricular growth as compared to hearts from untreated piglets. In summary, these results demonstrate that the reduced rate of left ventricular growth in vivo and the reduced rate of ribosome formation and protein synthesis in the left ventricle in vitro after enalapril treatment of piglets is not the result of an inhibitory effect of bradykinin on cardiac growth.
Mol Cell Biochem
PMID:Role of bradykinin in the antihypertrophic effects of enalapril in the newborn pig heart. 897 42

Numerous studies suggest that the renin angiotensin system (RAS) is involved in the development of cardiac hypertrophy. In the present study we produced cardiac hypertrophy in rats subjected to abdominal aortic banding and also induced cardiac regression by the administration of an angiotensin converting enzyme (ACE) inhibitor, enalapril, at 3, 10 and 30 mg/kg/day. Each drug was administered to the rats for 6 weeks from 6 weeks after aortic banding. The left ventricular weight significantly decreased at 10 and 30 mg/kg/day of enalapril as well as the systolic blood pressure. Using the reverse transcriptase polymerase chain reaction, the increased levels of ACE and AT1 mRNA were significantly inhibited in the aortic banding rats treated with the above concentrations of enalapril. The ACE activity in both the plasma and heart tissue preparations was significantly inhibited by enalapril. Similar observations were also seen after the administration of angiotensin type 1 receptor blockade, E-4177, into the aortic banding rats. The treatment with enalapril at 3 mg/kg/day did not reduce the left ventricular weight or the systolic blood pressure in the aortic banding rats. However, this low-dose treatment did significantly decrease the left ventricle to body weight ratio in the aortic banding rats without a reduction of the systolic blood pressure. Therefore, using the low-dose enalapril, the ACE activity in plasma was in part inhibited and the levels of ACE mRNA also decreased in the heart tissue of aortic banding rats, while the level of AT1 mRNA showed no such decrease. These results thus indicate that chronic ACE inhibitor at low doses has a beneficial effect on the regression in the pressure-induced cardiac hypertrophy. It is thus assumed that this effect may also contribute to the presence of an alternate pathway for the conversion of angiotensin I to angiotensin II which might also act as a possible mechanism for cardiac regression.
Mol Cell Biochem
PMID:Chronic low-dose treatment with enalapril induced cardiac regression of left ventricular hypertrophy. 897 63

Although increased deposition of collagen proteins has been described after myocardial infarction (MI), little is known of time-dependent transcriptional alteration of specific cardiac collagen sub-types as well as the degradative mechanisms for cardiac collagens in right and left ventricular myocardium remote to large left ventricular infarction. We sought to study collagen mRNA abundance and the deposition of specific collagen subtypes in noninfarcted left and right rat heart muscle at different times after MI. We also assessed the activity of different myocardial matrix metalloproteinases (MMP) using zymography to gain some information about degradative pathways for collagen. Furthermore, we assessed passive compliance properties of the right ventricle in experimental hearts. Finally we investigated the role of the renin angiotensin system in the collagen gene expression by administration of an angiotensin converting enzyme (ACE) inhibitor (ramipril) and an angiotensin II receptor type I antagonist (losartan) in experimental animals. We observed that the mRNA abundance of types I and III collagen were increased 3 days after myocardial infarction in both viable left and uninfarcted right ventricular tissues, that they peaked at 7-14 days, and were maintained at relatively high levels in the 28 and 56 days experimental groups. Stiffness of the right ventricular myocardium was significantly increased in the 56 days experimental group when compared to that of control values. These findings correlated with increased immunohistochemical staining patterns of different collagen species in the surviving right (and left) cardiac interstitium of 14, 28, and 56 day experimental cardiac groups. The elevation of fibrillar collagen mRNA abundance in noninfarcted muscle from ventricular chambers was not significantly altered after treatment of experimental animals with ramipril and losartan for up to 14 days. MMP activity was increased in viable left ventricle at 14, 28 and 56 days and at 14 days in the right ventricle in experimental animals when compared to controls. These results indicated that (1) activation of transcription of collagen types I and III gene occurs in acute and chronic MI, and that fibrillar collagen proteins are deposited in the noninfarcted cardiac interstitium after a lag period relative to increased corresponding mRNA abundance; (2) an increase in MMP activity in chronic experimental hearts indicates that increased collagen deposition may be due to an increment in collagen synthesis rather by reduced degradation of collagen, and that MMP activation may be important in remodeling of the noninfarcted cardiac stroma; (3) an increase of right ventricular stiffness was associated with increased deposition of collagen; (4) as losartan treatment is not associated with any normalization of elevated collagen mRNA abundance, the upregulation of collagen gene expression in this model is not mediated by AT1 receptor; and (5) the reduction of cardiac fibrosis mediated by ACE inhibition and losartan treatment may reside at the post-translational level in cardiac collagen metabolism.
Mol Cell Biochem 1996 Dec 06
PMID:Effect of ramipril and losartan on collagen expression in right and left heart after myocardial infarction. 897 79

Alterations in uterine nuclear and cytosolic estradiol (ER) and progesterone (PR) receptor concentration, activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), glucose-6-phosphate dehydrogenase (G-6-PDH) and lactate dehydrogenase (LDH), surface and transmission electron microscopy and histology in relation to the time of secretion of nidatory estrogen and the onset of endometrial sensitivity in the rat were investigated. A significant increase in plasma estradiol (E2) concentration in control rats was observed at 22.00 h on day 4 post-coitum, whereas progesterone (P) concentration increased at 17.00 h on day 4 and was maintained until 17.00 h on day 5. The period of high endometrial sensitivity (10.00 h on day 5) was characterized by elevated uterine cytosolic ER and nuclear and cytosolic PR concentration and POD activity, low columnar luminal epithelium with undulating surface and intercellular membranes, covered with short microvilli and pinopods, and containing numerous electron-transparent apical vesicles, mitochondria, polyribosomes, rough (RER) and smooth (SER) endoplasmic reticulum, well developed Golgi, few lysosomes and lipid droplets and loose edematous antimesometrial stroma. Inhibition in endometrial sensitivity by post-coital centchroman was associated with a marked depletion in uterine cytosolic ER and an increase in nuclear ER concentration, a decrease in POD and G-6-PDH activities, compact fibroblastic stroma, an increase in luminal epithelial cell height with decreased RER, SER, polyribosomes, Golgi, straightening of intercellular membranes, reduced surface undulations and absence of pinopods. Electron-transparent vesicles appeared flattened and clumped in the apical portion of cells, tight junctions were more prominent and lipid droplets were translucent. Nuclear and cytosolic PR and the pattern of secretion or plasma E2 and P remained unaffected. CAT, SOD and LDH activities, although high throughout pre-implantation, did not vary in relation to the secretion of nidatory estrogen, endometrial sensitivity or centchroman treatment.
J Steroid Biochem Mol Biol 1996 Oct
PMID:Uterine estradiol and progesterone receptor concentration, activities of certain antioxidant enzymes and dehydrogenases and histoarchitecture in relation to time of secretion of nidatory estrogen and high endometrial sensitivity in rat. 901 Mar 37

The efficacy of angiotensin converting enzyme (ACE) inhibitors is well known to prevent the formation of angiotensin II (Ang II) by these agents. The objective of the present study was to evaluate the hemodynamic, biochemical, and morphological responses to Ang II receptor blockade with E-4177, 3-[(2'-carboxybiphenyl-4-yl) methyl]-2-cyclopropyl-7-methyl 3H-imidazol[4,5-b] pyridine, in rats with a healing myocardial infarction that had been induced by the surgical occlusion of the left main coronary artery. The left ventricular weight increased 8 and 12 weeks after infarction in comparison to that in sham-operated rats. Among the rats with experimental infarction, treatment with E-4177 significantly decreased the left ventricular weight. Although the infarct size was not affected by E-4177, its administration ameliorated the elevated end-diastolic pressure and reduced the systolic pressure. The effects of this agent on the levels of Ang II type 1 (AT1) receptor mRNA and ACe mRNA were evaluated in the non-infarcted myocardium by reverse transcriptase polymerase chain reaction and binding assays. Treatment with E-4177 reduced both the elevated AT1 mRNA and the number of Ang II receptors, but not the ACE mRNA or ACE activity. While the receptor affinity remained unchanged with this agent, the collagen concentration was decreased. On the other hand, the depressed Na+/Ca2+ exchange activity was restored in the non-infarcted myocardium at 8 and 12 weeks after injury to the level seen in the sham-operated rats. These findings suggest that the AT1 receptor antagonist, E-4177, has a beneficial effect on the hemodynamics in spite of the lack of any improvement in the infarct size. These observations may be partly attributed to the prevention of angiotensin II formation during the period of post-infarction healing.
J Mol Cell Cardiol 1996 Mar
PMID:Regression of hypertrophy after myocardial infarction is produced by the chronic blockade of angiotensin type 1 receptor in rats. 901 34

The attenuation of myocardial stunning by the ACE inhibitor ramiprilat is prevented by cyclooxygenase inhibition with indomethacin. In the clinical setting of ischemia/reperfusion however, the cyclooxygenase inhibitor aspirin is widely used to prevent platelet aggregation. The present study therefore investigated whether aspirin in dosages sufficient to inhibit platelet aggregation interferes with the attenuation of myocardial stunning by ramiprilat. Fifteen dogs received either 1 mg/(kg.day) (group I, n = 7) or 10 mg/(kg.day) (group II, n = 8) aspirin orally for 1 week. Both dosages of aspirin inhibited ADP-induced platelet aggregation. The dogs were then anesthetized thoracotomized and subjected to 15 min LCx-occlusion and 4 h reperfusion. Before LCx-occlusion, groups I and II received ramiprilat (20 micrograms/kg, i.v.). Systemic hemodynamics, posterior myocardial blood flow (PMBF, colored microspheres) and wall thickening (PWT, sonomicrometry) of these groups were measured and data compared to placebo-controls (group III, n = 11) and dogs receiving only ramiprilat before LCx-occlusion (group IV, n = 11). Four dogs received 10 mg/(kg.day) aspirin without ramiprilat (group V). Mean aortic pressure was kept constant by an intra-aortic balloon, and heart rate did not change. PMBF was not different between the five groups. Under control conditions and during myocardial ischemia PWT was also not different. At 4 h reperfusion PWT was still depressed in group III (-5 +/- 20% of control) and group V (-23 +/- 6%) whereas PWT recovered to the same extent in groups I (46 +/- 23%), II (50 +/- 15%) and IV (58 +/- 18%) (all P < 0.05 v groups III and V). The attenuation of myocardial stunning by the ACE inhibitor ramiprilat is not prevented by aspirin in dosages which are nevertheless sufficient to inhibit platelet aggregation.
J Mol Cell Cardiol 1996 Mar
PMID:Aspirin does not prevent the attenuation of myocardial stunning by the ACE inhibitor ramiprilat. 901 43


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