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

Low renin hypertension (LRH), which accounts for 10-20% of patients with idiopathic "essential" hypertension, bears hormonal similarities to mineralocorticoid-induced hypertension, but elevated mineralocorticoid concentrations have not been found. Some patients with LRH have normal, rather than suppressed, plasma aldosterone concentrations, so that the ratio of aldosterone concentration to PRA (Aldo/PRA) is high, suggesting inappropriately increased aldosterone biosynthesis. We characterized the CYP11B2 gene that encodes the aldosterone synthase, P450c11AS, in hypertensive and control populations in a single clinic in Santiago, Chile. We directly sequenced the entire CYP11B2 gene in 12 patients with LRH, 2 high renin hypertensive controls, and 2 normotensive controls. All sequences were identical, except that 8 of 24 LRH alleles encoded arginine rather than lysine at position 173. The Arg173 and Lys173 variants were expressed in transfected MA-10 cells, and their ability to convert deoxycorticosterone to aldosterone was measured; the apparent Michaelis constant (Km) for Lys173 was 2.73 mumol/L; the Km for Arg173 was 2.53 mumol/L. The apparent maximal velocity (Vmax) for Lys173 was 6.5 x 10(-3) micrograms/mL.24 h; the Vmax for Arg173 was 7.8 x 10(-3) micrograms/mL.24 h. The first order rate constant, Vmax/Km was 2.38 for Lys173 and 3.08 for Arg173. As these values were not significantly different, we sought to determine whether Arg173 is a polymorphism linked to LRH. We examined position 173 in 52 unselected patients with idiopathic hypertension and 55 normotensive controls by PCR amplification of CYP11B2 exons 3-5 followed by digestion with Bsu361, which digests the Arg173 sequence, but not the Lys173 sequence. More of the hypertensive alleles (39 of 104, 37.5%) than normotensive alleles (25 of 110, 22.5%) carried Arg173 (chi 2 = 5.57; P < 0.02). Most of the Arg173 alleles (31 of 72, 43.1%) were from hypertensive patients with Aldo/PRA below 30, whereas only 5 of 24 (20.8%) Arg173 alleles were found in patients with Aldo/PRA greater than 30 (chi 2 = 3.79; P = 0.05) Thus, the ARg173 variant of CYP11B2 may be linked to LRH in Chilean patients.
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PMID:Genetic variation in P450c11AS in Chilean patients with low renin hypertension. 895 40

Aldosterone synthase (AS) is encoded by the CYP11B2 gene, a candidate for familial hypertension. CYP11B2 was previously mapped to chromosome 8q but its precise localization is necessary for genetic studies of hypertension. The present study reports the genetic mapping of the human CYP11B2 gene by radiation hybrid (RH) analysis, the isolation of a bacterial artificial chromosome (BAC) containing this gene and its physical mapping by fluorescent in situ hybridization (FISH). The CYP11B2 locus is on the most distal segment of the long arm of chromosome 8, proximal to the microsatellite polymorphic marker D8S1704. This location, which was confirmed by FISH, is approximately 60cM telomeric to the currently listed human gene locus (chromosome 8q21-22) and corresponds to cytogenetic band 8q24.3. The BACs containing the gene and a high-resolution map of the CYP11B2 locus are useful for genetic studies of hypertension and other endocrine disorders.
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PMID:Human CYP11B2 (aldosterone synthase) maps to chromosome 8q24.3. 950 70

Aldosterone is synthesized in extra-adrenal tissues such as blood vessels and brain. Damage to blood vessels could play a crucial role in perpetuating hypertension. In this study, we determined both aldosterone production and aldosterone synthase gene-CYP11B2 mRNA expression in vessels of spontaneously hypertensive rats (SHR). The results showed that aldosterone was overproduced in the vasculature of SHR, by means of ex vivo mesenteric artery perfusion, HPLC, and RIA, and that CYP11B2 mRNA expression was upregulated in aortas of SHR, confirmed by RT-PCR and Southern blot.
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PMID:Aldosterone overproduction and CYP11B2 mRNA overexpression in vessels of spontaneously hypertensive rats. 969 Dec 10

Anomalies in either of the tightly linked genes encoding the enzymes CYP11B1 (11beta-hydroxylase) or CYP11B2 (aldosterone synthase) can lead to important changes in arterial pressure and are responsible for several monogenically inherited forms of hypertension. Mutations in these genes or their regulatory regions could thus contribute to genetic variation in susceptibility to essential hypertension. To test this hypothesis, we performed 2 complementary studies of the CYP11B1/CYP11B2 locus in essential hypertension. After characterizing a DNA contig containing the CYP11B1 gene and mapping the gene in the Centre d'Etudes du Polymorphisme Humain reference panel of families, we performed a linkage study with 292 hypertensive sibling pairs and a highly informative microsatellite marker near CYP11B1. We also analyzed the association of 2 frequent biallelic polymorphisms of the CYP11B2 gene, 1 in the promoter at position -344 (-344C/T) and the other, a common gene conversion in intron 2, with hypertension in 380 hypertensive patients and 293 normotensive individuals. Statistical analyses did not show significant linkage of the CYP11B1 microsatellite marker to hypertension. No positive association with hypertension was found with the gene conversion in intron 2, but a positive association with hypertension was found with the -344T allele. The hypertensive and normotensive samples differed significantly in both genotype (P=0.023) and allele frequencies (P=0.010). Our data suggest a modest contribution of the CYP11B2 gene to essential hypertension.
Hypertension 1998 Aug
PMID:Structural analysis and evaluation of the aldosterone synthase gene in hypertension. 971 43

In this study the known promoter region of P450aldo gene (CYP11B2) was investigated in patients with idiopathic hyperaldosteronism, a disease characterised by hypertension due to aldosterone oversecretion. We amplified the 2.2 kb promoter region of 6 patients and 7 controls from the same ethnic population by PCR and sequenced the product. Thirteen polymorphic sites were found. Of the most significant, one was within a predicted CRE and another previously described polymorphic site was located in a putative SF-1 binding site. To elucidate the allelic distribution of the polymorphisms, the PCR products were cloned and both alleles for each patient were sequenced. As the same alleles and allele combinations were found in hypertensive patients as well as in normal subjects, it was concluded that none of the polymorphisms was responsible for hyperaldosteronism.
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PMID:Aldosterone synthase gene in patients suffering from hyperaldosteronism. 988 92

Low-renin hypertension is characterized by a high ratio of aldosterone to plasma renin activity (ALD/PRA), which may suggest inappropriately increased aldosterone biosynthesis. The genes for the enzymes involved in aldosterone synthesis may contribute to low-renin hypertension. We investigated the associations between genetic variations of CYP11B2 (aldosterone synthase) T(-344)C and hypertension in 482 Japanese subjects. Subjects older than 50 years with a blood pressure <140/85 mm Hg were considered normotensive (n=227 subjects), and subjects younger than 65 years old with a BP >160/95 mm Hg were considered hypertensive (n=255 subjects). The frequency of the TC+CC genotypes in the normotensive group was significantly lower than in the hypertensive group. Logistic analysis on 482 subjects revealed that body mass index, gender, and the genotype of CYP11B2 T(-344)C were significantly associated with hypertension. ALD and PRA were assessed in 97 subjects with hypertension, and the TC+CC genotypes were significantly associated with higher ALD/PRA. Sixty-five subjects with hypertension were assessed by 24-hour ambulatory blood pressure monitoring, and the frequency of nondippers (a difference in mean blood pressure of <10% between the daytime [6 AM to 9 PM] and nighttime [9 PM to 6 AM] hours) was significantly higher in subjects with the TC+CC (hetero+homo mutation) genotype than in subjects with the TT (wild-type) genotype. Echocardiographic assessment (n=136) revealed that the ratio of left ventricular end-diastolic dimension to height tended to be higher in subjects with the TC+CC genotype than in subjects with the TT genotype. The present study suggests that the (-344)C allele of the CYP11B2 gene may be a genetic marker for low-renin hypertension in Japanese.
Hypertension 1999 Jan
PMID:Genetic polymorphism of CYP11B2 gene and hypertension in Japanese. 993 Nov 15

Idiopathic hyperaldosteronism (IHA) is characterized by hypertension with excessive production of aldosterone, potassium loss, and suppression of the renin-angiotensin system. We compared activity of aldosterone synthase and expression of CYP11B2 messenger RNA (mRNA) in mononuclear leukocytes (MNL) from patients with IHA to findings in leukocytes from patients with aldosterone-producing adenoma and normal controls. Aldosterone synthase activity was estimated from conversion of [14C]deoxycorticosterone to [14C]aldosterone. Levels of CYP11B2 mRNA were determined by competitive PCR. In the same subjects, we sought the chimeric CYP11B1/CYP11B2 that is candidate gene for glucocorticoid-remediable hyperaldosteronism. Southern blot analysis and a long PCR method were used to detect the chimeric gene. Direct sequencing of the CYP11B2 also was performed. No chimeric genes or mutations in the coding region of the CYP11B2 were found in genomic DNA from these patients. However, both aldosterone synthase activity and CYP11B2 mRNA expression were greater in mononuclear leukocytes of patients with IHA than those of patients with aldosterone-producing adenoma or controls. These results suggest that regulatory factors of the CYP11B2 gene, e.g. unidentified aldosterone-stimulating substances or abnormalities in the promoter region of the CYP11B2 gene in patients with IHA resulting in oversecretion, may cause overexpression of mRNA of CYP11B2.
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PMID:Genetic analysis of aldosterone synthase in patients with idiopathic hyperaldosteronism. 1032 92

The aims of this study were to search for the role of cholic acid in the regulation blood pressure of humans and rats and to investigate the effects of cholic acid on the production of vascular aldosterone and corticosterone in rats. Levels of serum total bile acids were measured by an enzymic spectrophotometeric method in normal controls, patients with essential hypertension, and in Wistar and spontaneously hypertensive rats. Levels in essential hypertension (7.3+/-3.4 micromol/l, n = 88) were higher than those of normal subjects (4.9+/-3.3 micromol/l, n = 86), and levels in SHR (13.9+/-3.8 micromol/l, n = 11) were slightly increased, but not significantly different from Wistar rats (10.4+/-5.1 micromol/l, n = 12). Male Wistar rats received cholic acid 80 mg/kg/day, orally, for 30 days, and blood pressure was monitored by a pressure transducer. Systolic blood pressure increased in Wistar rats treated with cholic acid compared to control rats. Mesenteric artery perfusion ex vivo was performed, and pressor responses to norepinephrine were determined in Wistar rats. The pressor responses to norepinephrine in mesenteric arteries treated with cholic acid were significantly increased. The perfusate from the mesenteric arteries was collected and applied to a Sep-Pak C 18 cartridge column for reverse phase high performance liquid chromatography, and levels of both aldosterone and corticosterone were determined by radioimmunoassay. Levels of aldosterone were decreased but those of corticosterone increased in the perfusate from arteries treated with cholic acid. Reverse transcriptase polymerase chain reaction showed that cholic acid inhibited the expression of 11beta-HSD2 and CYP11B2 mRNA in mesenteric arteries. These results reveal that cholic acid is able to induce hypertension and provide evidence that cholic acid inhibits the transcription of both 11beta-HSD2 and CYP11B2 in vasculature, leading to lower aldosterone and higher corticosterone production in vessels and increased vasoconstrictor responses to norepinephrine.
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PMID:Effects of cholic acid on blood pressure and production of vascular aldosterone and corticosterone. 1039 86

This study is to confirm the role of glycyrrhizin on blood pressure and to test the effects of glycyrrhizin on production of vascular aldosterone and corticosterone in rats. Male Wistar rats received glycyrrhizin (Sigma) 200 mg/kg/day p.o. for 5 weeks, and blood pressure was monitored by a pressure transducer. Systolic blood pressure significantly increased in Wistar rats treated with glycyrrhizin compared to that without glycyrrhizin. Mesenteric artery perfusion ex vivo and pressor responses to norepinephrine were performed. The pressor responses to norepinephrine in mesenteric arteries treated with glycyrrhizin were significantly increased. The perfusate from the mesenteric arteries was collected and applied to a Sep-Pak C 18 cartridge column, used for reverse-phase high-performance liquid chromatography, and measured for both aldosterone and corticosterone by radioimmunoassay. Levels of aldosterone were decreased but those of corticosterone increased in perfusate from arteries treated with glycyrrhizin. RT-PCR showed that glycyrrhizin inhibited the expression of 11beta- HSD2 and CYP11B2 mRNA in mesenteric arteries. These results confirm that glycyrrhizin is able to induce hypertension, and provide evidence that it inhibits the transcriptions of both 11beta-HSD2 and CYP11B2 in the vasculature, leading to lower aldosterone and higher corticosterone production in vessels, and increased vasoconstrictor responses to norepinephrine.
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PMID:Effects of glycyrrhizin on production of vascular aldosterone and corticosterone. 1047 21

The renin-angiotensin-aldosterone system plays an important role in blood pressure regulation by influencing salt-water homeostasis and vascular tone. The purpose of the present study was to search for associations of single nucleotide polymorphisms on 3 major candidate genes of this system with the plasma concentrations of the corresponding renin-angiotensin-aldosterone system components considered as quantitative phenotypes. Genotyping was performed in 114 normotensive subjects for different variants of the angiotensinogen (AGT) gene (C-532T, G-6A, M235T), the angiotensin I-converting enzyme (ACE) gene [4656(CT)(2/3)], the aldosterone synthase (CYP11B2), and the type 1 angiotensin II receptor (AT1R) gene (A1166C) by hybridization with allele-specific oligonucleotides (ASO) or enzymatic digestion of polymerase chain reaction products. Plasma levels of AGT, ACE, angiotensin II (Ang II), aldosterone, and immunoreactive active renin were measured according to standard techniques. Platelet binding sites for Ang II were analyzed by the binding of radioiodinated Ang II to purified platelets. B(max) and K(D) values of the Ang II binding sites on platelets of each individual were calculated to examine a possible relationship between these parameters and the AT1R genotype. A highly significant association of the ACE 4656(CT)(2/3) variant with plasma ACE levels was observed (P<0.0001). ANOVA showed a significant effect of the AGT C-532T polymorphism on AGT plasma levels (P=0.017), but no significant effect was detectable with the other AGT polymorphisms tested, such as the G-6A or the M235T. A significant effect association was also found between the C-344T polymorphism of the CYP11B2 gene and plasma aldosterone levels, with the T allele associated with higher levels (P=0.02). No genotype effect of the AT1R A1166C polymorphism was detected either on the B(max) or the K(D) value of the Ang II receptors on platelets.
Hypertension 1999 Sep
PMID:Genotype-phenotype relationships for the renin-angiotensin-aldosterone system in a normal population. 1048 88


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