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)

The vascular effects of angiotensin converting enzyme inhibitors are mediated by the inhibition of the dual action of angiotensin converting enzyme (ACE): production of angiotensin II and degradation of bradykinin. The deleterious effect of converting enzyme inhibitors (CEI) on neonatal renal function have been ascribed to the elevated activity of the renin-angiotensin system. In order to clarify the role of bradykinin in the CEI-induced renal dysfunction of the newborn, the effect of perindoprilat was investigated in anesthetized newborn rabbits with intact or inhibited bradykinin B2 receptors. Inulin and PAH clearances were used as indices of GFR and renal plasma flow, respectively. Perindoprilat (20 microg/kg i.v.) caused marked systemic and renal vasodilation, reflected by a fall in blood pressure and renal vascular resistance. GFR decreased, while urine flow rate did not change. Prior inhibition of the B2 receptors by Hoe 140 (300 microg/kg s.c.) did not prevent any of the hemodynamic changes caused by perindoprilat, indicating that bradykinin accumulation does not contribute to the CEI-induced neonatal renal effects. A control group receiving only Hoe 140 revealed that BK maintains postglomerular vasodilation via B2 receptors in basal conditions. Thus, the absence of functional B2 receptors in the newborn was not responsible for the failure of Hoe 140 to prevent the perindoprilat-induced changes. Species- and/or age-related differences in the kinin-metabolism could explain these results, suggesting that in the newborn rabbit other kininases than ACE are mainly responsible for the degradation of bradykinin.
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PMID:Role of bradykinin in the neonatal renal effects of angiotensin converting enzyme inhibition. 945 May 2

Pulmonary arterial hypertension is common in patients with SSc. Fig. 1 shows the diagnostic and therapeutic approach to PAH in SSc. Doppler echocardiography may suggest the diagnosis, but RHC is necessary to confirm PAH and to measure vasoreactivity. Therapy is directed at the underlying connective tissue disease. Vasoreactive patients often benefit from therapy with high-dose calcium-channel [figure: see text] blockers, but most patients are not vasoreactive. Intravenous epoprostenol and oral endothelin-1 receptor antagonists improve hemodynamic measurements and symptoms in SSc-associated PAH. The therapy of right ventricular failure is focused on vasodilators, inotropes, and diuretics with careful attention to avoiding systemic hypotension. The scleroderma pulmonary-renal syndrome and the scleroderma renal crisis are distinct syndromes with different clinical presentations, histopathologic manifestations, treatments, and outcomes. The scleroderma pulmonary renal syndrome is an autoimmune vasculitis of kidney and lung associated with normal blood pressure. Treatment is supportive, and prognosis is dismal. In contrast, scleroderma renal crisis is associated with systemic hypertension, onion skinning of afferent arterioles, and response to ACE inhibition and renal replacement therapy. Pericardial effusions are common but only occasionally lead to tamponade. Esophageal dysmotility is often associated with aspiration, leading to pulmonary fibrosis, pneumonia, or ARDS. Diffuse bowel involvement may result in pseudo-obstruction, bacterial overgrowth, or malabsorption. Prokinetic agents, antibiotics, and parenteral nutrition may be required.
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PMID:Life-threatening complications of systemic sclerosis. 1241 43

Albuminuria increases the risk of cardiovascular events in patients with essential hypertension and diabetic subjects. The heritability (h2) of albuminuria in multiplex hypertensive families is unknown. We calculated the familial aggregation of urine albumin:creatinine ratio (ACR) and performed a genome-wide scan to assess for loci contributing to ACR in participants enrolled in the Hypertension Genetic Epidemiology Network (HyperGEN). To perform the genome scan, we analyzed genotype results from 2589 individuals from 805 families in the Family Blood Pressure Program. ACR and covariates were available in 1727 individuals (mean age, 57.1 years). Estimates of h2 were obtained by using variance component methodology as implemented in the SOLAR software package. Linkage was tested between 387 markers spanning the genome at an average interval of 9.32 cM, using SOLAR multipoint analysis. The h2 of log urine ACR was 0.49 (P<1x10(-7)) after controlling for significant main and interactive effects of age, gender, race, body mass index, blood pressure, and use of ACE inhibitors or angiotensin-2 receptor blockers. The genome-wide scan revealed a maximum LOD score of 2.73 on chromosome 19 (robust corrected LOD, 2.40; P=0.0009) at marker D19S591 and a LOD score of 2.0 on chromosome 12 (robust corrected LOD, 1.75; P=0.005) at marker PAH. These analyses demonstrate the marked heritability of urine ACR in families enriched for the presence of members with essential hypertension. They suggest that a gene(s) associated with urinary ACR may be present on human chromosomes 19 and 12.
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PMID:A genome-wide scan for urinary albumin excretion in hypertensive families. 1292 55

Population genetic survey of the indigenous populations of the Marii El Republic, represented by the two major ethnographic groups of Maris, Meadow (five samples from Morkinsk, Orshansk, Semursk, Sovetsk, and Zvenigovsk districts) and Mountain (one sample from Gornomariisk district) Maris, was carried out. All Mari groups were examined at nine polymorphic DNA loci of nuclear genome, VNTR(PAH) (N = 422), STR(PAH) (N = 152), VNTR(ApoB) (N= 294), VNTR(DAT1) (N = 363), VNTR(eNOS) (N = 373), ACE (N = 412), IVS6aGATT (N = 513), D7S23(KM.19) (N = 494), and D7S8 (N = 366). Allele and genotype frequency distribution patterns were obtained for individual samples and ethnographic groups, as well as for the ethnic group overall. In each of six Mari samples examined, the deficit of heterozygotes was observed, i.e., the mean observed heterozygosity was lower than the expected one. The indices of mean heterozygosity, Hs = 0.455, and interpopulation differentiation, FST = 0.0024, for the Mari gene pool were obtained using a set of DNA markers analyzed. Analysis of the genetic distances and between population differentiation (FST) showed that the main part of genetic diversity in Maris was determined by the differentiation between the populations of Meadow Maris. The contribution of the differences between the ethnographic groups of Mountain and Meadow Maris to the ethnic gene pool was small. It is suggested that the main role in the formation of the Mari gene pool is played by the geographic factor.
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PMID:[Analysis of polymorphism at nine nuclear genome DNA loci in maris]. 1658 10

The major objective of this work was to explore the quantitative structure-activity relationship (QSAR) of hydroxyl-substituent Schiff bases in protecting human erythrocytes against 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH)- induced hemolysis, in which 10 Schiff bases including 4-phenyliminomethylphenol (PIH); 4-((4-hydroxybenzylidene) amino)phenol (PAH); 2-methoxy-4-((4-hydroxyphenylimino)methyl)phenol (PMH); 4-((furan-2-ylmethylene)amino) phenol (FAH); 4-((4-N,N-dimethylaminobenzylidene)amino)phenol (PDH); 2-((4-N,N-dimethylaminobenzylidene)amino) phenol (ODH); 2-(naphthalene-1-yliminomethyl)phenol (NAH); 2-(benzyliminomethyl)phenol (BPH); 1,4-di((2-hydroxyphenylimino) methyl)benzene (DOH); 1,4-di((4-hydroxyphenylimino)methyl)benzene DPH, were available for this in vitro experimental system. The results revealed that the radical-scavenging activity of the --OH attached to the para position of methylene in Schiff base was much lower than that attached to the ortho position of the N atom. The large conjugate system and low steric hindrance in the framework of Schiff base benefit the Schiff base to trap radicals. Meanwhile, since a Schiff base, even without any substituent, can also play an antioxidative role in this experimental system, the QSAR results suggest that hydroxyl-substituent Schiff bases are potential drugs in the treatment of radical-related diseases, and provide more information for designing novel drugs.
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PMID:Quantitative structure-activity relationship of hydroxyl-substituent Schiff bases in radical-induced hemolysis of human erythrocytes. 1760 39

Genetic structure of Southern and Northern ethnographic groups of the Udmurt population from six regions of the Republic of Udmurtia has been studied. All the samples were examined using ten polymorphic DNA loci: VNTR/PAH, VNTR/ApoB, VNTR/DAT1, VNTR/eNOS, ACE, CCR5delta32, KM19, IVS6a, THOI, and FABP2. Allelic and genotype frequencies were estimated for each of the six populations. The average heterozygosity for these ten polymorphic loci varied from 0.47 in Udmurts from Glazovskii region to 0.53 in Udmurts from Malopuginskii region. The level of genetic variation (F(ST)) between populations of Udmurts was 0.0048. Ethnographic subdivision of the population into Northern and Southern Udmurts is in good agreement with the values of genetic distances and phylogenetic analysis.
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PMID:[Population study of the Udmurt population: analysis of ten polymorphic DNA loci of the nuclear genome]. 1763 63


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