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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The renin angiotensin system (RAS) is involved in blood pressure control and water/sodium metabolism. The genes encoding the proteins of this system are candidate genes for essential hypertension. The RAS involves four main molecules: angiotensinogen, renin, angiotensin I-converting enzyme, and the angiotensin II type 1 receptor (encoded by the genes AGT, REN, DCP1, and AGTR1, respectively). We performed a molecular screening over 17,037 bp of the coding and 5' and 3' untranslated regions of these genes, from three to six common chimpanzees. We identified 44 single-nucleotide polymorphisms (SNPs) in chimpanzee samples, including 18 coding-region SNPs, 5 of which led to an amino acid replacement. We observed common and different features at various sites (synonymous, nonsynonymous, and noncoding) within and between the four chimpanzee genes: (1) the nucleotide diversity at noncoding sites was similar; (2) the nucleotide diversity at nonsynonymous sites was low, probably reflecting purifying selection, except for the AGT gene; (3) the nucleotide diversity at synonymous sites, which was dependent on the G+C content at the third position of the codon, was high, except for the AGTR1 gene. Comparison of the chimpanzee SNPs with those previously reported for humans identified 119 sites with fixed differences (including 62 coding sites, 17 of which resulted in amino acid differences between the species). Analysis of polymorphism within species and divergence between species shed light on the evolutionary constraints on these genes. In particular, comparison of the pattern of mutation at polymorphic and fixed sites between humans and chimpanzees suggested that the high G+C content of the DCP1 gene was maintained by positive selection at its silent sites. Finally, we propose 68 ancestral alleles for the human RAS genes and discuss the implications for their use in future hypertension-susceptibility association studies.
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PMID:Human-chimpanzee DNA sequence variation in the four major genes of the renin angiotensin system. 1101 71

A peptide fraction having activity against angiotensin I-converting enzyme (ACE) was separated from the peptic digest of protein prepared from wakame (Undaria pinnatifida) by ion-exchange chromatographies and gel-filtration. Fractions with high ACE inhibitory activity were combined and further chromatographed on a reverse-phase column to yield four tetrapeptides with ACE inhibitory properties. These tetrapeptides were identified by sequence analysis and fast atom bombardment mass spectrometry as Ala-Ile-Tyr-Lys (IC(50): 213 microM), Tyr-Lys-Tyr-Tyr (64.2 microM), Lys-Phe-Tyr-Gly (90.5 microM), and Tyr-Asn-Lys-Leu (21 microM). Each tetrapeptide was synthesized and its antihypertensive activity was determined after oral administration in spontaneously hypertensive rats. The blood pressure significantly decreased after tetrapeptide ingestion. The present study demonstrated that dietary wakame may have beneficial effects on hypertension.
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PMID:Identification of an antihypertensive peptide from peptic digest of wakame (Undaria pinnatifida). 1109 Nov

An insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene has been described in chromosome 17q23 of the human genome. Subjects with the genotype DD have markedly higher plasma ACE levels than those with genotype II; although ACE concentration in plasma is not rate-limiting for the production of angiotensin II, it has been suggested that the renin-angiotensin system may have an enhanced role in cardiovascular homeostasis in subjects with DD genotype or D allele. Meta-analysis confirmed the association of the D allele with an increased risk of myocardial infarction and stroke, but these relations are still uncertain with longevity and renal deterioration. Otherwise, I allele seems to be related with an improved response to physical training. The I/D polymorphism of the ACE gene is not a marker for any form of hypertension, though some conflicting results have been described. Nevertheless this polymorphism may have an influence on the antihypertensive response, particularly when using ACE inhibitors (ACEI). For example, blood pressure normalization with captopril in patients suffering from cardiac failure would be more effective in II genotype; conversely, both regression in left ventricular hypertrophy and improvement in diastolic filling would be greater after long-term treatment with enalapril in patients with essential hypertension and DD genotype. Conflicting results were also described using ACEI as a renoprotective therapy. This review therefore supports the justification for further evaluation in appropriately powered studies.
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PMID:Angiotensin I-converting enzyme gene polymorphism and drug response. 1109 39

This study focused on two genes that have previously been implicated in hypertension and may influence renal sodium handling, adducin, and angiotensin I-converting enzyme (ACE). We compared their polymorphic frequencies and interaction in patients with essential hypertension (n=128) and individually age- and gender-matched normotensive control subjects. The alpha-adducin G460W polymorphism was genotyped by DNA amplification and restriction digestion. The ACE I/D polymorphism was assayed by a triple-primer method, with a "nested" polymerase chain reaction primer situated completely within the insertion sequence of the I: allele. The distributions of genotypes and alleles for the two polymorphisms were not significantly different between the case and control populations, and the cross-classification of cases by alpha-adducin and ACE genotype gave a distribution similar to that of control subjects. We have previously reported that the distributions of genotypes for two linked polymorphisms in the aldosterone synthase gene (one in the steroidogenic factor-1 [SF-1] binding site and the other an intronic conversion [IC]) were significantly different between this cohort of essential hypertensives and matched control subjects. The cross-classification of cases by alpha-adducin and SF-1, alpha-adducin and IC, ACE and SF-1, and ACE and IC genotype gave a distribution similar to that of control subjects. Hence, no evidence was found to suggest an association between either the alpha-adducin G460W or the ACE I/D polymorphism and hypertension in a careful case-control study. Furthermore, the alpha-adducin G460W, ACE I/D, and aldosterone synthase SF-1 and IC polymorphisms do not appear to interact in our hypertensive population.
Hypertension 2000 Dec
PMID:alpha-adducin and angiotensin I-converting enzyme polymorphisms in essential hypertension. 1111 13

Oligopeptides of 1 KDa or less were obtained by hydrolysis of chicken egg yolks with a crude enzyme, and by dialysis with a semipermeable membrane filter. Since the extracted peptides had an inhibitory action on the activity of angiotensin I-converting enzyme (ACE) in vitro, they were orally administered at 20, 100 and 500 mg/kg body weight to spontaneously hypertensive rats (SHR) for 12 weeks to analyze the physiological role on cardiovascular functions. The administered oligopeptides suppressed the development of hypertension at all dosages. After 12 weeks at 500 mg/kg body weight, the values for systolic, mean, and diastolic blood pressure were approximately 10% less in SHRs administered than controls. Furthermore, serum ACE activity of the peptide-administered groups was significantly lower than that of the control group in a dose-related manner. Our results imply that oligopeptides extracted from hen's egg yolks could potentially suppress the development of hypertension in SHR, and this effect might be induced by the inhibition of ACE activity.
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PMID:Antihypertensive effect of ACE inhibitory oligopeptides from chicken egg yolks. 1116 71

Angiotensin I-converting enzyme (ACE) activity was analyzed in human urine collected from mild hypertensive untreated patients. DEAE-cellulose chromatography using linear gradient elution revealed two forms of angiotensin I-converting enzyme, eluted in the conductivity of 0.75 and 1.25 mS. The fractions of each conductivity were pooled and submitted to direct gel filtration in an AcA-34 column, and the apparent molecular weights of urinary ACEs were estimated as 90 kDa (for ACE eluted in 0.75 mS) and 65 kDa (for ACE eluted in 1.25 mS). Both enzymes have a K(i) of the order of 10(-7) M for the specific inhibitors studied, and are able to hydrolyze luteinizing hormone-releasing hormone and N-acetyl-Ser-Asp-Lys-Pro as described for N-domain ACE. By Western blot analysis, both peaks were recognized by ACE-specific antibody Y4, confirming the molecular weight already described. A plate precipitation assay using monoclonal antibodies to the N-domain of ACE showed that both forms of ACE binds with all monoclonal antibodies to the active N-domain ACE, suggesting that these forms of human urine ACEs resemble the N-fragment of ACE. The HP2 ACE (65 kDa) is similar to low molecular weight (LMW) ACE from normal subjects, and the HP2 ACE (90 kDa) is different from high molecular weight (190 kDa) and LMW (65 kDa) normal ACEs. The 90 kDa ACE could have an important role in development of hypertension. It will be fundamental to elucidate the molecular mechanism responsible for the genesis of this isoform.
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PMID:Angiotensin converting enzymes from human urine of mild hypertensive untreated patients resemble the N-terminal fragment of human angiotensin I-converting enzyme. 1116 34

The conversion of angiotensin I (AT-I) to angiotensin II (AT-II) by angiotensin I-converting enzyme (ACE) is a key step in the action of angiotensins. ACE is constitutively expressed in endothelial cells, but can also be detected at low levels in smooth muscle cells (SMC). Furthermore, in rats the ACE activity can be induced in SMC in vivo by experimental hypertension or vascular injury and in vivo by corticoid treatment. This study was therefore undertaken to evaluate the conversion of AT-I and its subsequent effects in SMC in basal conditions and after stimulation by dexamethasone. Using rat and human SMC, showed that dexamethasone induced ACE expression and that this enzyme was functional, leading to AT-II-dependent intracellular signaling. A fourfold increase in phospholipase C activity in response to AT-I was observed in dexamethasone-activated SMC compared with quiescent SMC. This effect of dexamethasone on signal transduction is dependent on ACE activity, whereas AT-II receptor parameters remain unchanged. The action of AT-I was blocked by an AT1 receptor antagonist, suggesting that it was mediated by AT-II. Similarly, dexamethasone-induced ACE expression was present in human SMC, and calcium signaling was mobilized in response to AT-I in activated human cells. Experiments performed with cocultures of endothelial cells and SMC in a Transwell system showed that the response to AT-I was limited to the compartment where AT-I was localized, suggesting that AT-I does not pass through the endothelial cell barrier to interact with underlying SMC. Our data suggest that in rat, as in human SMC, the conversion of AT-I into AT-II and the signal transduction in response to AT-I are ACE expression-dependent. In addition, the present findings show that this SMC response to AT-I is endothelium-independent, supporting the idea of a local generation of AT-II in the vascular wall.
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PMID:Endothelium-independent conversion of angiotensin I by vascular smooth muscle cells. 1129 69

Kinins are vasoactive peptide hormones that can confer protection against the development of hypertension. Because their efficacy is greatly influenced by the rate of enzymatic degradation, the activities of various kininases in plasma and blood of spontaneously hypertensive rats (SHR) were compared with those in normotensive Wistar-Kyoto rats (WKY) to identify pathogenic alterations. Either plasma or whole blood was incubated with bradykinin (10 microM). Bradykinin and kinin metabolites were measured by high-performance liquid chromatography. Kininase activities were determined by cumulative inhibition of angiotensin I-converting enzyme (ACE), carboxypeptidase N (CPN), and aminopeptidase P (APP), using selective inhibitors. Plasma of WKY rats degraded bradykinin at a rate of 13.3 +/- 0.94 micromol x min(-1) x l(-1). The enzymes ACE, APP, and CPN represented 92% of this kininase activity, with relative contributions of 52, 25, and 16%, respectively. Inclusion of blood cells at physiological concentrations did not extend the activities of these plasma kininases further. No differences of kinin degradation were found between WKY and SHR. The identical conditions of kinin degradation in WKY and SHR suggest no pathogenic role of kininases in the SHR model of genetic hypertension.
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PMID:Pathways of bradykinin degradation in blood and plasma of normotensive and hypertensive rats. 1129 20

Hypertension leads to renal disease through a series of mechanisms that seem to be exaggerated in African-Americans, who have a higher prevalence of both hypertension and end-stage renal disease than whites. Renal disease itself leads to hypertension, which in turn can contribute to progression of renal disease. Although there are numerous mechanisms involved in the process of renal disease progression, the renin-angiotensin system plays a major role as determined by the beneficial response to angiotensin I-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (AT II blockers) of reduced rate of progression in a variety of clinical and experimental renal diseases. Macromolecular trafficking across the glomerulus leading to proteinuria plays a significant role in progression of chronic renal disease. Reversal of this abnormality and reduced stress on capillary walls may be the major mechanisms of beneficial action of ACEIs and AT II blockers in halting renal disease progression.
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PMID:Role of hypertension in the progression of chronic renal disease. 1136 24

During development of hypertension in spontaneously hypertensive (SHR) rats, the activity of adrenal nitric oxide synthase (NOS) was investigated. SHR and Wistar-Kyoto (WKY) rats were studied at different ages: 3-4, 7-8 and 12-13 weeks after birth. Basal NOS activity was measured by the ability of homogenate to convert [3H]-L-arginine to [3H]-L-citrulline. At all ages, SHR rats exhibited 50-60% reduction in NOS activity when compared to age-matched WKY rats. In a following study, SHR rats (12-13 weeks) were treated chronically with the angiotensin I-converting enzyme inhibitors (ACE-I) captopril or enalapril, or the AT1-receptor antagonist losartan (2 x 25, 10 and 60 mg/kg per day for 10 days, respectively). The total NOS activity and protein expression of NOS isoenzymes from adrenals were determined. The basal NOS activity and protein expression of neuronal NOS (nNOS) was significantly increased in treated SHR rats when compared to control rats. The isoforms endothelial NOS and inducible NOS were undetectable. We conclude that impaired NO synthesis in the adrenal glands of SHR rats may contribute to the onset and maintenance of hypertension. The upregulation of nNOS protein in the adrenal glands may be one of the mechanisms by which ACE inhibitors and AT1-receptor antagonists by restoring the NO synthesis, mediate their antihypertensive effects.
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PMID:Angiotensin-converting enzyme inhibitors and AT1-receptor antagonist restore nitric oxide synthase (NOS) activity and neuronal NOS expression in the adrenal glands of spontaneously hypertensive rats. 1138 39


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