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)

We report here the protective effect of the angiotensin converting enzyme inhibitors captopril and ramiprilat against damage due to oxygen free radicals on aortic endothelium in a superfusion cascade system. Oxygen free radicals were generated by electrolysis of Krebs solution. Acetylcholine was infused through the donor aortic segment and relaxation of the detector aortic ring was used to indicate the release of endothelium-derived relaxing factor (EDRF). The percentage of relaxation before and after electrolysis was compared to calculate the relaxation index. Electrolyzed Krebs solution impaired the release of EDRF, as shown by a reduction in the relaxation index with a concomitant decrease in the tissue levels of superoxide dismutase and 6-keto PGF1 alpha and increase in malondialdehyde in the donor vessel. Captopril (100 microM), 15 microM ramiprilat and 30 nM iloprost had a protective effect as shown by a significantly smaller reduction in the relaxation index and the level of 6-keto PGF1 alpha and by an attenuation of the production of malondialdehyde. In addition, 1 microM indomethacin almost eliminated the protection by captopril. We conclude that both the SH-containing angiotensin-converting enzyme inhibitor captopril and the non-SH-containing ramiprilat, as well as iloprost, a stable analog of prostacyclin, can protect rabbit aortic endothelium against damage due to oxygen free radicals. The mechanism of such protection may be partly associated with the facilitation of the release of prostacyclin and consequent reduction in lipid peroxidation.
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PMID:Prostacyclin-mediated protection by angiotensin-converting enzyme inhibitors against injury of aortic endothelium by free radicals. 137 80

1. We have studied the contractile activity of the 39 amino acid precursor of endothelin-1 (ET-1), big endothelin-1 (big ET-1), on human isolated bronchi. The contribution of the metalloproteases, neutral endopeptidase (NEP) and angiotensin converting enzyme (ACE), in the presence or absence of the epithelium lining, by use of specific inhibitors, was also evaluated on the effects of big ET-1. 2. Big ET-1 elicited a potent contraction of human isolated bronchus. The -log EC50 value for big ET-1 was 7.53 +/- 0.08 (n = 11) and Emax 78.5 +/- 3.8% (% of ACh 3mM). 3. Incubation of human isolated bronchi with the NEP inhibitor phosphoramidon (10(-5) M) induced a rightward shift of the concentration-response curve induced by big ET-1 (10(-9) M to 3 x 10(-7) M). Similar results were observed when human bronchi were incubated with thiorphan (10(-5) M), but the shift to the right was significantly less (P less than 0.01) than that observed in the case of phosphoramidon (-0.35 +/- 0.05 vs -0.67 +/- 0.07 log unit). 4. The two inhibitors of angiotensin I converting enzyme (ACE), captopril or enalapril diacid, did not affect the concentration-response curve for contraction induced by big ET-1. 5. When the epithelium was removed, a leftward shift of the concentration-response curve of big ET-1 (10(-9) M to 3 x 10(-7) M) was observed. Incubation of human isolated bronchi with phosphoramidon or thiorphan (10-5M) or with enalapril diacid or captopril did not modify the leftward shift of the concentration-response curve for big ET-1 after epithelium removal.6. These results suggest that big ET-1 elicits potent contractile activity in the human isolated bronchus and that its effect is the consequence of the conversion to ET-1 by a phosphoramidon-sensitive metalloprotease which, although different from NEP and ACE, appears to be similar to the endothelinconverting enzyme (ECE) described in other studies in animals.
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PMID:Contractile activity of big endothelin-1 on the human isolated bronchus. 139 87

The function of the endothelium is impaired in hypertension. In spontaneously hypertensive rats (SHR), acetylcholine-induced relaxation is decreased and serotonin-induced constriction is increased. The goal of our study was to evaluate the effect of a long-term treatment with cilazapril, a new angiotensin converting enzyme inhibitor, or hydralazine, a vasodilator, on the endothelium-dependent responses in aorta of SHR. Wistar-Kyoto rats were used as normotensive reference. Isolated aortic rings with or without endothelium were suspended in organ chambers. The rings with intact endothelium were contracted with norepinephrine. Acetylcholine-induced relaxation was markedly enhanced by cilazapril treatment. The tension achieved at maximal relaxation was 8 +/- 4% of norepinephrine contraction in the cilazapril-treated SHR versus 55 +/- 5% in the untreated SHR (p less than 0.001). Hydralazine had no significant effect. The effect of serotonin was also markedly modified by cilazapril. In untreated SHR, serotonin induced the release of a vasoconstrictor substance by the endothelium as assessed by the ratio of maximal tension induced by serotonin in rings with endothelium over maximal tension in rings without endothelium, which was greater than 1. This ratio was reversed in cilazapril-treated SHR but not in hydralazine-treated SHR. Captopril had effects similar to cilazapril. Finally, evaluation of carotid arteries showed that cilazapril also prevented morphological changes of the intima in SHR (i.e., infiltration by mononuclear cells). We conclude that angiotensin converting enzyme inhibitors prevent the functional and morphological alterations in endothelium that are found in hypertension and speculate that this action might participate in their antihypertensive effect.
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PMID:Effects of angiotensin converting enzyme inhibitors and of hydralazine on endothelial function in hypertensive rats. 222 54

To assess factors responsible for phasic behavior of renal blood flow in essential hypertension, we applied an analytic method based on the estimation of power spectral density to xenon transit through the kidney and examined the renal vasodilator response to a range of agents in 53 normal subjects and 53 patients with essential hypertension. The renal vasodilator response to the calcium channel blocking agent diltiazem, but not the response to alpha-adrenergic blockade (phentolamine) or angiotensin converting enzyme inhibition (teprotide or captopril), was associated with a significant reduction in the amplitude of renal vasomotion. Acetylcholine, a vasodilator that acts through the release of a vasorelaxant factor or factors from endothelium, induced an unanticipated increase in renal vasomotion. These observations further dissociate factors responsible for basal renal vascular tone and periodic changes in renal vascular tone and raise the possibility that abnormalities in the flux of calcium into renal arterioles contribute to increased renal vasomotion in essential hypertension.
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PMID:Renal vasomotion in essential hypertension: influence of vasodilators. 273 40

We investigated the effects of inhibition of both nitric oxide (NO) synthesis and angiotensin converting enzyme (ACE) on agonist-induced relaxations in the coronary system. Chronically instrumented conscious dogs (n = 4) were prepared for the measurement of coronary blood flow (CBF), coronary diameter of the left circumflex artery (LCX), mean arterial blood pressure (MAP) and heart rate (HR). Intracoronary infusions of acetylcholine, adenosine and bradykinin were performed after intracoronary pretreatment of either vehicle, L-NAME (6 mg.kg-1), captopril (1 mg.kg-1) or both L-NAME+captopril. Acetylcholine bradykinin and adenosine caused dose-dependent increases in CBF and LCX. HR increased concomitantly. Captopril potentiated the vasodilating effects of bradykinin and acetylcholine on LCX and CBF significantly (P < or = 0.05) and those of adenosine slightly. L-NAME caused vasoconstriction, hypertension and bradycardia. The effects of acetylcholine on CBF were abolished during L-NAME treatment while bradykinin and adenosine responses were markedly reduced. When captopril and L-NAME were given simultaneously, the vasodilator responses to bradykinin but not to acetylcholine or adenosine were partially restored (P < or = 0.05). We conclude that in vivo, (a) adenosine possibly elicits endothelium-dependent dilation; (b) adenosine and bradykinin act in part independently of the L-arginine/NO pathway; (c) vasodilation to acetylcholine is potentiated by acute ACE inhibition via NO-dependent mechanisms.
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PMID:Coronary vasodilation to acetylcholine, adenosine and bradykinin in dogs: effects of inhibition of NO-synthesis and captopril. 829 69

We postulated that nitric oxide (NO)-mediated endothelial function would be improved by acute and short-term treatment with an angiotensin converting enzyme (ACE) inhibitor in patients with type I diabetes mellitus, in whom endothelial function is depressed. Nine type I diabetic patients and eight healthy subjects underwent forearm blood flow measurement using strain gauge plethysmography during intraarterial infusion of incremental doses of endothelium-dependent (acetylcholine [ACh]) and endothelium-independent (sodium nitroprusside [SNP]) vasodilators. Pretreatment ACh responses were depressed in diabetic patients relative to the normal subjects (P < 0.05). No difference between the groups was evident in response to SNP. Acute ACE inhibition (with intrabrachial enalaprilat) enhanced ACh responses in the diabetic patients (P < 0.005), with a further improvement evident after 1 mo of oral therapy with enalapril (P < 0.001) when ACh responses were normalized. ACE inhibition did not affect SNP responses. We conclude that acute administration of the ACE inhibitor, enalaprilat, enhances NO-mediated endothelial function in type I diabetic patients, with further improvement evident after 4 wk of enalapril therapy.
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PMID:Improvement in endothelial function by angiotensin converting enzyme inhibition in insulin-dependent diabetes mellitus. 923 16

Non-adrenergic non-cholinergic (NANC) contraction of airway smooth muscle has been observed in some but not all animal species. The aim of this study was to investigate the NANC-contractile responses in bovine and swine trachea. Proximal and distal bovine and swine trachea were cut in strips and placed in 10 ml organ baths equilibrated in Krebs Henseleit (KH) solution and electrically stimulated (10 sec, 60 V, 2 ms, 4, 10 and 30 Hz). Contractile frequency response curves performed in the presence of the muscarinic antagonist, atropine (100 mM), the angiotensin converting enzyme inhibitor, captopril (1 microM) and the neutral endopeptidase inhibitor, thiorphan (1 microM), added 30 min prior to electrical field stimulation (EFS). In some tissues, incubated with atropine thiorphan and captopril, were also evaluated the effects of a pretreatment with capsaicin (10 microM) or a selective NK1 receptor antagonist, SR 14033 (100 nM) added to the baths 30 min prior to EFS. Bovine and swine proximal and distal tracheal preparations contracted in a frequency-dependent manner to EFS (4, 10 and 30 Hz). Some experiments were also performed with substance P (0.1 nM to 1 microM) in absence or in presence of SR 14033 (10 nM or 100 nM). At the maximum frequency tested (30 Hz), the contractile response elicited in bovine proximal and distal preparations was 194.5 +/- 17.1% and 229.7 +/- 24.1%, of ACh (100 microM), respectively. Similarly, the contractile response elicited by EFS (30 Hz) in swine proximal and distal preparations was 187.2 +/- 12.1% and 181.6 +/- 9.2% of ACh (100 microM), respectively. In tissues incubated with atropine, a significant decrease in smooth muscle sensitivity to EFS was observed (P < 0.05). When tissues were pretreated with captopril and thiorphan, a significant increase in the contractile response to EFS (30 Hz) was observed in all tested tissue preparations (bovine, proximal 210.1 +/- 14.4%, distal 264.3 +/- 16.2%; swine, proximal 199.3 +/- 14.9%, distal 206.3 +/- 16.2%, P < 0.05). In the presence of atropine, captopril and thiorphan a significant increase in the contractile response was observed in bovine and swine distal preparations compared with tissues incubated with atropine only (P < 0.05). These effects were antagonized by a pretreatment with a selective NK1 receptor antagonist, SR 14033. A pretreatment with capsaicin statistically (P < 0.05) enhanced EFS-induced contraction in all tested preparations respect to tissues incubated with atropine, thiorphan and captopril. Substance P induced a concentration dependent contraction of bovine and swine isolated tracheal preparations which was antagonized by a pretreatment with a selective NK1 receptor antagonist, SR 14033. No significant difference in the contractile potency (EC50) nor in maximum response (Emax) was observed to exogenously administered substance P between proximal and distal tracheal preparations. These data suggest that NANC contractile responses are present in bovine and swine trachea and are more evident in distal airways.
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PMID:Evidence for non-adrenergic non-cholinergic contractile responses in bovine and swine trachea. 942 42

Airway hyperreactivity (AHR) is an important characteristic feature of asthma. Recently, it has been recognized that airway inflammation underlies the phenomenon of AHR. Kinins such as bradykinin (BK) and kallidin (KD) have been implicated as mediators of airway inflammatory diseases. Tachykinins such as substance P (SP) and neurokinin A (NKA) produce a variety of effects on the airways. These effects include changes in bronchomotor tone, vasodilatation, increase in vascular permeability and facilitation of the release of other transmitters. Non-cholinergic responses are due to release of neuropeptides such as tachykinins from sensory nerve endings. Kinins and tachykinins have been implicated in neurogenic inflammation. The O3 exposure (3 ppm, 30 min) induced AHR to ACh in guinea pigs. The O3-induced AHR was significantly enhanced by pretreatment with captopril, a kininase II inhibitor. Infusion of subthreshold dose of BK and KD developed AHR to ACh. The O3-induced AHR was significantly inhibited by pretreatment with capsaicin. Infusion of the subthreshold dose of SP and NKA developed an AHR to ACh. The KD-induced AHR was inhibited by pretreatment with capsaicin. Kinins and tachykinins may be therefore involved in the O3-induced AHR, and kinins may act through tachykinin intervention on the O3-induced AHR.
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PMID:[Involvement of kinin and tachykinin in airway hyperreactivity]. 961 9

1. Hypoxic pulmonary hypertension in rats (10% O2, 4 weeks) is characterized by changes in pulmonary vascular structure and function. The effects of the angiotensin converting enzyme inhibitor perindopril (oral gavage, once daily for the 4 weeks of hypoxia) on these changes were examined. 2. Perindopril (30 mg kg-1 d-1) caused an 18% reduction in pulmonary artery pressure in hypoxic rats. 3. Structural changes (remodelling) in hypoxic rats included increases in (i) critical closing pressure in isolated perfused lungs (remodelling of arteries <50 microm o.d.) and (ii) medial wall thickness of intralobar pulmonary arteries, assessed histologically (vessels 30 - 100 and 101 - 500 microm o.d.). Perindopril 10 and 30 mg kg-1 d-1 attenuated remodelling in vessels < or = 100 microm (lungs and histology), 30 mg kg-1 d-1 was effective in vessels 101 - 500 microm but neither dose prevented hypertrophy of main pulmonary artery. 3 mg kg-1 d-1 was without effect. 4. Perindopril (30 mg kg-1 d-1) prevented the exaggerated hypoxic pulmonary vasoconstrictor response seen in perfused lungs from hypoxic rats but did not prevent any of the functional changes (i.e. the increased contractions to 5-HT, U46619 (thromboxane-mimetic) and K+ and diminished contractions to angiotensins I and II) seen in isolated intralobar or main pulmonary arteries. Acetylcholine responses were unaltered in hypoxic rats. 5. We conclude that, in hypoxic rats, altered pulmonary vascular function is largely independent of remodelling. Hence any drug that affects only remodelling is unlikely to restore pulmonary vascular function to normal and, like perindopril, may have only a modest effect on pulmonary artery pressure.
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PMID:Perindopril, an angiotensin converting enzyme inhibitor, in pulmonary hypertensive rats: comparative effects on pulmonary vascular structure and function. 1060 19

The effect of chronic treatment with the angiotensin converting enzyme inhibitor, temocapril, on prevention of endothelial dysfunction was evaluated in an experimental model of diabetes mellitus. Endothelium-dependent relaxation to acetylcholine was impaired while endothelium-independent relaxation to nitroglycerin was unaltered in diabetic aortic ring segments. Treatment of diabetic animals with temocapril prevented the impaired endothelium-dependent relaxation without altering responses to nitroglycerin. Acetylcholine-induced relaxation was largely due to nitric oxide (NO)-mediated relaxation; however, a small but significant portion of relaxation in aortic rings from temocapril-treated diabetic rats was resistant to inhibition by the nitric oxide synthase (NOS) inhibitor, L-nitroarginine.
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PMID:Temocapril, an angiotensin converting enzyme inhibitor, protects against diabetes-induced endothelial dysfunction. 1096 53


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