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)

A double-blind, randomized, cross-over, placebo-controlled study was carried out to determine the extent and duration of potentiation of the action of bradykinin introduced intradermally by a long-acting novel angiotensin converting enzyme (ACE) inhibitor, trandolapril. The investigations were performed in a temperature and humidity-controlled laboratory. Intradermal injections of 1 microgram, 2.5 micrograms and 5 micrograms of bradykinin and normal saline (as control) were made into the forearm skin of eight healthy normotensive male volunteers aged 21-33 years (mean 28 years) at baseline, 2, 4, 8, 24, 48, 72 and 96 hours after either 2 mg trandolapril or placebo given orally. Skin blood flow outside the induced weal was monitored by laser Doppler flowmetry (mean of recordings at four sites adjacent to the weal within the flare area). Flare area and weal volume were also measured. Trandolapril reduced the mean arterial pressure. However, there was no evidence that this activity was associated with a potentiation of the cutaneous action of bradykinin. In conclusion, it would appear that potentiation of the action of bradykinin may not be an important contributing factor to the fall in total peripheral vascular resistance associated with ACE inhibition in humans in the control of hypertension.
Postgrad Med J 1992 Sep
PMID:Absence of potentiation of the skin response to intradermal bradykinin by a long-acting angiotensin converting enzyme inhibitor, trandolapril, at conventional antihypertensive dosage in human volunteers: a double-blind, randomized, cross-over, placebo-controlled trial. 148 May 37

As the major regulator of arterial blood pressure and sodium balance, the renin axis supports normotension or hypertension via angiotensin-mediated vasoconstriction and angiotensin plus aldosterone-induced renal sodium retention. In this endocrine servo control, renal renin is released by hypotension or salt depletion; conversely, with hypertension or volume excess, plasma renin activity falls to zero. Accordingly, any renal renin secretion is abnormal in the face of arterial hypertension. Human hypertensive disorders comprise a spectrum of abnormal vasoconstriction-volume products (renin-sodium profiles). Excess plasma renin activity for the sodium balance is created by nephron heterogeneity in which a subpopulation of ischemic nephrons hypersecretes renin and retains sodium. This excess renin impairs adaptive natriuresis of neighboring normal nephrons. Research defining the pivotal role of vascular cytosolic calcium for transducing sodium or renin-mediated vasoconstriction explains the selective value of calcium antagonists for correcting the sodium-volume-mediated, and beta-blockers or angiotensin converting enzyme inhibitors for correcting renin-mediated, arteriolar vasoconstriction. The renin precursor prorenin appears to be physiologically active, causing selective vasodilation that offsets renin-mediated vasoconstriction. Overactivity of prorenin may be involved in the hyperperfusion vascular injuries of diabetes mellitus and toxemias. Prorenin underactivity may facilitate renin-mediated ischemic vascular injury. In essential hypertension, undue plasma renin activity is powerfully and independently associated with heart attack risk. Conversely, patients with low renin activity are protected from heart attack despite higher blood pressures and greater age. Also, renin or angiotensin administration consistently causes vascular injury in the heart, brain, and kidneys of animals. These data suggest new potentials for the prevention of cardiovascular sequelae (heart attack and stroke) by using explicit strategies to curtail plasma renin activity.
Hypertension 1992 Sep
PMID:Lewis K. Dahl Memorial Lecture. The renin system and four lines fo hypertension research. Nephron heterogeneity, the calcium connection, the prorenin vasodilator limb, and plasma renin and heart attack. 151 45

Soluble angiotensin-binding protein (sABP) is a 75-kDa cytosolic protein that binds angiotensins and its analogues with high affinity. In this study, the primary structure of porcine sABP is determined by cDNA cloning. Based on the partial amino acid sequences of sABP tryptic fragments, fully degenerate oligonucleotides were synthesized, and used as primers for polymerase chain reactions to amplify the corresponding sABP cDNA fragment from porcine liver first-strand cDNA. By using initially the polymerase chain reaction product and later partial cDNA clones as probes, porcine heart and liver cDNA libraries were screened, and several positive clones were obtained including one covering the entire coding region. From the cDNA sequence, an open reading frame that encodes sABP as a 704-amino acid protein with molecular mass of 80,800 daltons is predicted. No significant homology was seen between sABP and other proteins in GenBank and NBRF data bases, including the angiotensin-related proteins such as angiotensin converting enzyme, renin, and AT1 angiotensin II receptor. Northern blot analysis of poly(A)+ RNA revealed that the mRNA for sABP is expressed as 5.3- and 2.8-3.2-kilobase transcripts. These transcripts are generated by the use of alternative polyadenylation signals. Within the 3'-untranslated region of the cDNA sequence downstream from the polyadenylation signals for smaller transcripts, a porcine short interspersed repetitive element (SINE) was found; only the longer 5.3-kilobase transcript had the SINE sequence.
J Biol Chem 1992 Sep 05
PMID:Molecular cloning of porcine soluble angiotensin-binding protein. 151 39

Proteolytic removal of amino-terminal octapeptides from mitochondrial intermediate proteins is a required step for a subgroup of nuclear-encoded mitochondrial precursors and is specifically catalyzed by mitochondrial intermediate peptidase (MIP). We recently reported the purification of MIP from rat liver and showed that the enzyme is a monomer of 75 kDa. We now report the sequence of a full-length rat MIP cDNA. This cDNA codes for a protein of 710 amino acids, including an amino-terminal mitochondrial leader peptide of 33 residues. The region surrounding the mature MIP amino terminus shows a cleavage site typically recognized by the general mitochondrial processing peptidase (MPP). In vitro synthesized MIP precursor is cleaved to mature MIP by purified MPP, and thus MIP is not required for its own proteolytic maturation. Comparison of the deduced MIP sequence with other sequences in the GenBank data base reveals two important similarities. The first is to a sequence encoding a putative MIP homologue in the recently reported sequence of yeast chromosome III. The putative yeast protein is predicted to be 712 amino acids long and includes a putative 23-residue mitochondrial leader peptide also with a MPP processing site. It shows 47% similarity and 24% identity to rat MIP. The second similarity is to members of a subfamily of metallopeptidases that includes rat metalloendopeptidase EC 3.4.24.15 and two bacterial proteases, oligopeptidase A and dipeptidyl carboxypeptidase. A region of greater than 50% similarity over 400 residues between MIP and these proteins is centered around the sequence motif HEXXH, typical of zinc metallopeptidases.
Proc Natl Acad Sci U S A 1992 Sep 01
PMID:Sequence analysis of rat mitochondrial intermediate peptidase: similarity to zinc metallopeptidases and to a putative yeast homologue. 151 64

The effects of angiotensin II (AII) blockade were compared with the effects of angiotensin converting enzyme inhibition in rats with reduced nephron number. Rats were subjected to five-sixths renal ablation and divided into four groups with similar values for blood pressure and serum creatinine after 2 wk. Group 1 then served as untreated controls, while group 2 received the AII receptor antagonist MK954 (which has previously been designated DuP753), group 3 received the converting enzyme inhibitor enalapril, and group 4 received a combination of reserpine, hydralazine, and hydrochlorothiazide. Micropuncture and morphologic studies were performed 10 wk later. Converting enzyme inhibition, AII receptor blockade, and the combination regimen were equally effective in reversing systemic hypertension (time-averaged systolic blood pressure: group 1, 185 +/- 5 mmHg; group 2, 125 +/- 2 mmHg; group 3, 127 +/- 2 mmHg; group 4, 117 +/- 4 mmHg). Micropuncture studies showed that glomerular transcapillary pressure was reduced significantly by converting enzyme inhibition and by AII blockade but not by the combination regimen (delta P: group 1, 49 +/- 1 mmHg; group 2, 42 +/- 1 mmHg; group 3, 40 +/- 2 mmHg, group 4, 47 +/- 1 mmHg). Reduction of systemic blood pressure was associated with the development of markedly less proteinuria and segmental glomerular sclerosis in rats receiving enalapril and MK954 but not in rats receiving the combination regimen (prevalence of glomerular sclerotic lesions: group 1, 41 +/- 4%; group 2, 9 +/- 1%; group 3, 9 +/- 1%; group 4, 33 +/- 6%). These results indicate that the effects of converting enzyme inhibition on remnant glomerular function and structure depend on reduction in AII activity and are not attributable simply to normalization of systemic blood pressure.
J Clin Invest 1992 Sep
PMID:Angiotensin II receptor blockade limits glomerular injury in rats with reduced renal mass. 152 31

Administration of the pyrrolizidine alkaloid monocrotaline (MCT) to rats results in hypertensive pulmonary vascular disease characterized by a structurally based increase in pulmonary vascular resistance and right ventricular hypertrophy. Alterations in lung angiotensin converting enzyme activity in MCT-treated rats have suggested a role for angiotensin II (AII) in the pathogenesis of this model of hypertensive pulmonary vascular disease. To determine if increases in AII contribute to the development of pulmonary hypertension in MCT-treated rats, we examined the effect of chronic administration of the nonpeptide AII receptor antagonist Losartan on indices of pulmonary hypertension, Losartan (DuP 753; 10 mg/kg s.c.) administration for 21 days did not prevent the development of hypertensive pulmonary vascular disease in MCT-treated rats. However, 18 hr after the last dose of Losartan, AII (0.1 micrograms/kg i.v.)-induced pressor responses were inhibited by 63% in Losartan-treated rats. Losartan administration in MCT-treated rats did not prevent increases in pulmonary artery pressure or development of right ventricular hypertrophy. Additionally, increases in medial arterial thickness in pulmonary artery vessels (less than 50 microns and 50-100 microns external diameter) from MCT-treated rats were still evident in Losartan-treated rats. However, Losartan administration decreased medial pulmonary artery thickness of 50 to 100 microns external diameter vessels in control rats. These results demonstrate that AII. acting at the AT1 receptor subtype, does not contribute to pulmonary hypertension in this animal model.
J Pharmacol Exp Ther 1992 Sep
PMID:Angiotensin II and monocrotaline-induced pulmonary hypertension: effect of losartan (DuP 753), a nonpeptide angiotensin type 1 receptor antagonist. 152 21

Inhibitors of two zinc metallopeptidases, angiotensin I converting enzyme (ACE) and neutral metalloendopeptidase-24.11 (EP-24.11), are antihypertensive agents. In this issue of Hypertension, Genden and Molineaux report that yet another peptidase inhibitor, metalloendopeptidase-24.15, EC 3.4.24.15 (EP-24.15), lowers blood pressure in normotensive rats. In this editorial we discuss the possible role of kinins as common mediators of part of the vasodepressor action of these peptidase inhibitors. Genden and Molineaux report that the marked fall in blood pressure caused by the EP-24.15 inhibitor is almost abolished by a kinin receptor antagonist, supporting the hypothesis that kinins play a role in the regulation of normal blood pressure. We have confirmed that the EP-24.15 inhibitor used by these investigators lowers blood pressure. Up to now, EP-24.15 has not been implicated in in vivo metabolism of kinins. Although a number of kininases have been identified, our own previous work indicated that the metabolic pathway responsible for clearing kinins from the circulation involves the action of kininase II (angiotensin I converting enzyme) and renal peptidases. Nevertheless, the main metabolic pathway involved some other unidentified enzyme, since in these experiments disappearance of kinins from the circulation was only marginally reduced by a "cocktail" of inhibitors of ACE, EP-24.11, and carboxypeptidase N. It could be that EP-24.15 is involved in kinin metabolism. However, a number of questions need to be answered with regard to the mechanism by which the EP-24.15 inhibitor lowers blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1991 Sep
PMID:Zinc metallopeptidase inhibitors. A novel antihypertensive treatment. 188 49

The functional state of the angiotensin system (the activity of the angiotensin converting enzyme--ACE) was studied in different rat brain regions during disturbance of the integrative activity of CNS after frontal lobectomy. The most prominent increase of the ACE activity (in four times) on the ninth day after lobectomy was detected in crown cortex and hippocamp. Considerable differences were discovered in striatum, thalamus and hypothalamus also. The variations of the ACE activity were not shown in the medulla oblongata and midbrain. It is possible to conclude, that ACE activity alternations have regional disposition and functional dependence.
Biull Eksp Biol Med 1991 Sep
PMID:[Changes in the activity of angiotensin converting enzyme in the structures of the rat brain after frontal lobectomy]. 166 Jul 37

For the application of restriction endonuclease analysis in typing and identifying leptospira, we selected some serovars and isolates, and analysed preliminarily their DNA with four restriction enzymes, EcoR I, Bgl II, Hha I, and Hind III. The DNA samples were isolated from the reference strains and isolates as follows: Serovar lai 56601, 017 (the virulent strain for PDH model of guinea pig), Serovar autumnalis 56606, Serovar manhao II 67020, and isolates 87112 and 87369. Each 2 micrograms of DNA was digested with 20mu of restriction enzyme at 37 degrees C for 2h and electrophoresed in 0.8% agarose gel. The gels were stained in ethidium bromide and photographed with UV light. In our experiments, apparently different restriction patterns of serovar lai 017 were observed with four restriction enzymes. Serovar lai, serovar autumnalis and serovar manhao II showed different patterns with EcoR I, especially in high molecular regions. We also observed in serovar lai 017 a distinct 10.5kb band which was obscure in 56601, the reference strain of serovar lai, after EcoR I digestion. The three serovars showed some delicate differences in Hind III restriction pattern. The two isolates from Apodemus agrarius in Sichuan (1987) 87112 and 87369 had patterns identical to those of serovar lai 56601, 017 with EcoR I, and 87112 also had a pattern identical to 56601, 017 with Hind III. Our results indicate that selected three serovars can be identified by analysis of their DNA with EcoR I and Hind III. It is suggested that restriction endonuclease analysis be a good method in typing and identify leptospira and in studying the differences of special DNA molecules.
Hua Xi Yi Ke Da Xue Xue Bao 1991 Sep
PMID:[Analysis of leptospiral deoxyribonucleic acids by restriction endonucleases]. 166 Aug 46

Paraquat is a herbicide known to cause pulmonary edema in its acute toxic phase. Many investigators showed that paraquat induces morphological changes of alveolar epithelial cells even in its early phase. Controversy still exists, however, as to whether pulmonary vascular endothelial cells are also morphologically vulnerable to paraquat. To test the direct toxicity and metabolic changes of pulmonary vascular endothelial cells after paraquat addition, porcine pulmonary artery endothelial cells (PPAEC) were cultured. Thrombin- or bradykinin-stimulated PGI2 production was enhanced significantly, and the angiotensin converting enzyme (ACE) activity of cell lysate of PPAEC was significantly suppressed after a 24-hour incubation with 10(-4) M of paraquat. No further thrombin-induced enhancement of PGI2 production was noted after a 48-hour incubation. The alterations in arachidonic acid metabolism and ACE activity mentioned above did not result from cytotoxicity of paraquat because LDH release into culture medium was not increased during 72 hours of incubation with paraquat. Longer incubation more than 48 hours, in turn, induces obvious toxic effects on PPAEC.
Nihon Kyobu Shikkan Gakkai Zasshi 1991 Sep
PMID:[Arachidonic acid metabolism and angiotensin converting enzyme activity by cultured porcine pulmonary artery endothelial cells are affected with paraquat]. 166 45


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