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)

Vasodilation in congestive heart failure is an established therapeutic principal. The ventricular unloading improves contractile geometry and thereby improves working conditions for the contractile element: myocardial oxygen consumption falls and myocardial efficiency improves. This effect is independent from the vasodilating substance employed; it is, however, dependent on the simultaneous induction of pre- and afterload reduction. Vasodilation improves regional perfusion. Differential improvement in organ bloodflow is related to the type of vasodilator employed. It seems essential for a therapeutic benefit that renal and coronary perfusion are improved and that shunt flow, especially with steal phenomena, is avoided. Skeletal muscle bloodflow improves only slowly under ACE-inhibitor therapy. It could be shown that the immediate vasodilation due to ACE inhibition is followed by a second phase of vasodilation, which may be related to the influence of ACE inhibition of intraarterial wall angiotensin converting enzyme. Another factor possibly responsible for the delayed response to vasodilation in congestive heart failure, may be functional and structural changes in skeletal muscle. Reversal of these changes requires time. Both factors - the vessel wall related mechanism, as well as changes in parenchymal structure and function - require prolonged periods of treatment until therapeutic benefit can be seen.
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PMID:[Therapy of heart failure with vasodilator agents]. 306 44

The authors have compared the short-term effect of two captopril (ACE inhibitor) preparations namely the Lopirin (SQUIBB) and Tensiomin (EGIS) and dihydralazine as well as placebo in 15 patients with severe heart failure (NYHA III-IV, class). In case of 8 patients with NYHA IV, functional class the short-term effect of the combined therapy of dihydralazine and Lopirin and dihydralazine and Tensiomin as well dihydralazine and placebo have been compared. The underlying disease was dilated cardiomyopathy (DCM) and ischaemic heart disease (IHD). At the end of the treatment with different drugs and placebo the clinical signs of heart failure (complaints and physical status) and the echo and mechanocardiographic parameters of left ventricular function were assessed. The parameters, apart from the clinical signs, have been evaluated in double blind fashion. Compared to placebo all the three drugs i.e. dihydralazine, Lopirin as well as Tensiomin have decreased significantly the NYHA classes, influenced favorably the non-invasive parameters of left ventricular function and decreased blood pressure. As to the dihydralazine, it improved the left ventricular ejection function and the clinical state of the patients with DCM in a higher degree than the two ACE inhibitors did. The effect of Tensiomin and Lopirin was the same in every respect. Both have influenced more favourable the complaints and physical state of patients with IHD than dihydralazine has. The left ventricular filling pressure, the double product (heart rate x wall tension) indicating the myocardial oxygen demand were more reduced in their effect than in that of dihydralazine. Unlike dihydralazine both decreased the heart rate. Administering one of the two ACE inhibitors to the dihydralazine beneficial additive effects have been experienced; the NYHA classes, the heart rate, the left ventricular wall tension and the double product diminished. The authors, on the bases of the results, consider Tensiomin and Lopirin as equivalent in their effect. In their opinion the administration of these drugs mean a new, efficient way of therapy, first of all in cases of heart failure caused by IHD. In the most severe cases they suggest a trial with the combined dihydralazine-ACE inhibitor therapy.
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PMID:Comparative study on the short-term effects of angiotensin converting enzyme inhibitors (Lopirin, SQUIBB and Tensiomin), and dihydralazine in chronic cardiac failure. 307 6

Hypoxia (10%-12% O2) preadaptation for 4-7 days effectively protects rats from oxygen toxicity. The present study was designed to investigate the hypothesis that the lung's microvascular endothelium shares in development of oxygen tolerance and therefore that endothelial metabolic function would be protected from oxygen toxicity by prior adaptation to hypoxia. Since pulmonary oxygen toxicity decreases lung capillary angiotensin converting enzyme (ACE) activity, we assayed converting enzyme active sites in an isolated perfused rat lung preparation as a marker for the development of oxygen toxicity and tolerance. Rats were exposed to air, hypoxia (10% O2 for 4 days), hyperoxia (greater than 95% O2 for 2 days) alone, or hypoxia followed immediately by hyperoxia. Lung vascular ACE content was quantitated by measuring the single pass binding of an iodinated-converting enzyme inhibitor, 125I-MK351A, a derivative of lisinopril. Hypoxia adaptation per se had no effect on ACE content reflected in normal 125I-MK351A binding, whereas hyperoxia exposure caused a significant decrease in lung vascular ACE. Hyperoxia-induced decreases in ACE content were prevented partially by hypoxia adaptation, indicating that ACE content on luminal endothelial surfaces was protected from oxygen toxicity. In isolated perfused lungs 125I-MK351A binding reflects development of oxygen tolerance after hypoxia preadaptation and suggests that lung endothelial metabolic function is protected from oxygen toxicity.
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PMID:Hypoxia-induced oxygen tolerance: maintenance of endothelial metabolic function. 320 27

The synthesis of a series of orally active, phosphinyloxyacyl proline inhibitors of angiotensin converting enzyme (ACE) is described. The in vitro and in vivo ACE inhibitory activities are reported for each compound. The structure-activity relationship for this series of compounds in relation to the carboxyalkyl dipeptide ACE inhibitors as well as other types of hydroxyphosphinyl-containing ACE inhibitors (e.g., the corresponding nitrogen and carbon isosteres) is discussed. Within an isosteric series of phosphorus-containing inhibitors based on the lysylproline terminal dipeptide sequence, only the phosphonates (oxygen isosteres) show a high level of oral activity. Optimum potency and oral activity in the phosphonate series occurs with the (phenylbutyl)- and n-hexylphosphonate side chains. An aminobutyl side chain in the P1' residue is an absolute requirement for full expression of oral activity. The most potent of these compounds, 8b (SQ 29,852), has intravenous and oral activities superior in potency to those of captopril in the normotensive rat.
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PMID:(Phosphinyloxy)acyl amino acid inhibitors of angiotensin converting enzyme (ACE). 1. Discovery of (S)-1-[6-amino-2-[[hydroxy(4-phenylbutyl)phosphinyl]oxy]-1-oxohexyl]-L -proline a novel orally active inhibitor of ACE. 333 20

The effects of 4 angiotensin I converting enzyme inhibitors (ACEI), captopril, enalapril, ramipril, and trandolapril, were investigated on regional myocardial blood flow (RMBF, radioactive microspheres) distribution in ischemic and nonischemic zones and on ST-segment elevation in ischemic zones during intermittent coronary artery occlusion in anesthetized dogs. The 4 ACEI inhibited plasma ACE activity to an almost similar extent. All similarly reduced systemic blood pressure, an effect related to a decrease in systemic vascular resistance. Heart rate and myocardial contractility were not affected, but myocardial oxygen consumption presumably decreased because of the reduction in afterload. RMBF and their distribution (between epicardial and endocardial layers and between nonischemic and ischemic zones) were not modified by ACEI. Coronary vascular resistance was slightly decreased in nonischemic zones. ACEI had no effect on ST-segment elevation in ischemic zones. Thus, in this experimental model, all ACEI exhibited the same profile, including no change in RMBF and affording no protection against ischemic injury.
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PMID:Effects of four angiotensin I converting enzyme inhibitors on regional myocardial blood flow and ischemic injury during coronary artery occlusion in dogs. 342 39

In order to evaluate the structural/functional roles of Met residues in an octadecapeptide pigment-dispersing hormone (PDH: Asn-Ser-Gly-Met-Ile-Asn-Ser-Ile-Leu-Gly-Ile-Pro-Arg-Val-Met-Thr-Glu-Ala- NH2), first described as light-adapting distal retinal pigment hormone (DRPH) from Pandalus, three analogs were synthesized: Nle4-PDH, Nle15-PDH, and Nle4,15-PDH. When tested for melanophore pigment-dispersing activity in destalked Uca, all three Nle-analogs were more potent than unsubstituted PDH. Performic acid oxidation caused a marked loss of potency of PDH, Nle4-PDH, and Nle15-PDH. The analog Nle4,15-PDH was resistant to oxidation and displayed 6-fold higher potency than PDH. Thus Met4 and Met15 are not essential for the PDH activity. The oxidation-induced loss of activity of unsubstituted PDH may result from introduction of oxygen (in methionine sulfone) and a consequent conformational change in the octadecapeptide.
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PMID:Substitution of norleucine for methionine residues in a crustacean pigment-dispersing hormone. 384 Aug 88

The response of serum angiotensin converting enzyme (ACE) activity to three grades of hypoxia was studied in two groups of human subjects. Hypoxic gas mixtures having oxygen concentrations of 14, 12.6 and 10.4% were breathed successively for a period of 10 min at each concentration. Venous blood was sampled at the end of each of the three periods and arterial oxygen saturation was recorded throughout the experiment. The subjects were selected as being 'good' or 'poor' acclimatizers according to their history of acute mountain sickness. There were five subjects in each group. Hypoxia resulted in a reduction in ACE activity in both groups, the reduction being linear with respect to arterial oxygen saturation. The reduction in ACE activity was greater in the good acclimatizer group as shown by a significantly greater slope of the response line of ACE activity to arterial oxygen saturation. The significance of this finding in relation to the mechanism underlying acute mountain sickness is discussed.
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PMID:Angiotensin converting enzyme response to hypoxia in man: its role in altitude acclimatization. 608 56

Because of evidence that angiotensin II may be necessary for pulmonary hypoxic vasoconstriction, we investigated the response to 3% oxygen breathing before and after the blockade of angiotensin I-converting enzyme with captopril. The left lungs of 6 cats were pump-perfused through the left pulmonary artery with blood withdrawn from the inferior vena cava. The animals were ventilated mechanically, and blood gases and pH were measured and maintained within normal limits. The pulmonary vascular resistance was calculated from measurements of pulmonary arterial pressure, left atrial pressure, and blood flow. Changes in pulmonary vascular resistance caused by 3% oxygen breathing, prostaglandin F2 alpha, angiotensin I, and angiotensin II were measured before and after captopril (20 mg/kg, i.v.). The pulmonary vascular response to hypoxia was not altered by the blockade of angiotensin II production. The responses to prostaglandin F2 alpha, and angiotensin II were unchanged as well, indicating that the vasoactivity of the pulmonary vessels was not altered. The response to angiotensin I was eliminated completely. These results indicate that angiotensin II is not necessary for, and does not alter, hypoxic pulmonary vasoconstriction in the cat.
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PMID:Feline hypoxic pulmonary vasoconstriction is not blocked by the angiotensin I-converting enzyme inhibitor, captopril. 616 1

Chronic hypoxic lung diseases are associated with abnormal blood pressure regulation. Because the lung is the principal site of angiotensin conversion and because hypoxia decreases converting enzyme activity, we examined whether angiotensin converting enzyme activity was impaired in lung disease. 12 dogs received a 6 wk course of aerosolized and intratracheal papain that produced moderate panlobular emphysema. These dogs and 24 control dogs were anesthetized and sampling catheters were placed under fluoroscopic control. Angiotensin conversion was measured by a blood pressure response bioassay. Pulmonary converting enzyme activity was also assessed by infusing bradykinin (BK) and using radioimmunoassay to measure the instantaneous clearance of BK and the concentration of BK in the pulmonary artery which first produced spillover of BK into left atrial blood. Angiotensin conversion was reduced in the emphysematous dogs to 81.1% (13.2 SD) from 92% (6 SD) in the control dogs (P < 0.01). Instantaneous clearance of BK in the emphysematous dogs was only slightly reduced (93%), despite reduction in their Pao(2) to 75 mm Hg, indicating that the greatest proportion of the perfused vascular bed was exposed to alveolar Po(2) of >90 mm Hg. However, the barrier to BK passage provided by the lung, and measured by the spillover level, was reduced (1/4) to (1/2) that observed in control animals. That the defect was promptly corrected by supplemental oxygen indicates that regional pulmonary vascular converting enzyme activity had been impaired by regional alveolar hypoxia, which permitted some peptide to pass through the lungs unmetabolized. Determination of peptide metabolism in the lungs may provide a useful measure of regional alveolar hypoxia and may lead to new ways of assessing lung injury.
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PMID:Impaired angiotensin conversion and bradykinin clearance in experimental canine pulmonary emphysema. 625 12

Changes in lung endothelial metabolic function, determined in vitro, have been proposed as sensitive indexes of hyperoxic lung damage. However, it is unclear whether these changes are also seen in vivo. We studied the possibility, using conscious rabbits in which jugular and carotid catheters had previously been placed under halothane anesthesia. Approximately 24 h later, test animals were exposed to normobaric hyperoxia (96 +/- 2%), while a second group was maintained in room air. Multiple indicator dilution methods were used to study (1) metabolism of 3H-benzoyl-phe-ala-pro (BPAP), a synthetic substrate for angiotensin converting enzyme (ACE), and (2) removal of 14C-5-hydroxytryptamine (5-HT) during a single transpulmonary passage in conscious animals. Determinations were made serially during exposure (room air or hyperoxia) or until death occurred in the oxygen-treated animals. Lungs of air-exposed animals hydrolyzed 81 +/- 2% of injected BPAP (0.1 to 0.15 nmoles) during a single passage. Percent metabolism was unaltered during the next 72 h. However, in test animals, ACE activity, as reflected by BPAP metabolism, was significantly reduced after 16 h of exposure to oxygen (77 +/- 2%, p less than 0.01) and continued to decrease to a nadir of 66 +/- 3% at 40 h. Single-pass lung uptake of 14C-5-HT (77 +/- 2%) was unchanged throughout the 72-h period in air-exposed rabbits. In test animals, 14C-5-HT removal decreased to 65 +/- 4% (p less than 0.01) after 24 h of oxygen exposure; 5-HT removal remained depressed compared with the 0 h control determination for the oxygen group at all subsequent measurement intervals. Light and electron microscopy of lungs from oxygen-exposed rabbits demonstrating reduced 5-HT removal and ACE activity at 24 h revealed normal endothelial and type I cell morphologic features. We conclude that exposure to 100% oxygen produced significant reduction in pulmonary 5-HT removal and BPAP metabolism prior to the onset of morphologic damage.
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PMID:Early detection of oxygen-induced lung injury in conscious rabbits. Reduced in vivo activity of angiotensin converting enzyme and removal of 5-hydroxytryptamine. 628 9


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