Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We tested if vitamin E, a fat-soluble antioxidant, prevents resistance vessel endothelial dysfunction caused by methionine-induced hyperhomocysteinemia in humans. Moderate elevations in plasma homocysteine concentrations are associated with atherosclerosis and hypertension. Homocysteine causes endothelial dysfunction possibly through several mechanisms. No previous study has tested if a fat-soluble antioxidant can prevent endothelial dysfunction caused by experimental hyperhomocysteinemia. Ten healthy subjects participated in a 2 x 2 factorial, double-blind crossover study, receiving L-methionine (100 mg/kg at -6 hours) or vehicle, with and without vitamin E (1,200 IU at -13 hours). Endothelial function of forearm resistance vessels was assessed using forearm blood flow responses to brachial artery administration of endothelium-dependent and endothelium-independent agents. Forearm resistance vessel dilatation to acetylcholine was significantly impaired 7 hours after methionine (placebo, 583 +/- 87% vs methionine 30 +/- 68%; p <0.05). Dilatation to bradykinin was also impaired (placebo, 509 +/- 54% vs methionine 289 +/- 48%; p <0.05). Methionine did not alter vasodilatation to the endothelium-independent vasodilators, nitroprusside, and verapamil. Methionine-induced impairment of resistance vessel dilatation to acetylcholine and bradykinin (p <0.05 vs placebo) was prevented by administration of vitamin E (acetylcholine, p = 0.004; bradykinin, p = 0.004; both vs methionine alone). Experimentally increasing plasma homocysteine concentrations by oral methionine rapidly impairs resistance vessel endothelial function in healthy humans and this effect is reversed with administration of the fat-soluble antioxidant, vitamin E.
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PMID:Effect of vitamin E on resistance vessel endothelial dysfunction induced by methionine. 1147 9

Numerous clinical and epidemiological studies have identified elevated homocysteine levels in plasma as a risk factor for atherosclerotic vascular disease and thromboembolism. Hyperhomocysteinemia may develop as a consequence of defects in homocysteine-metabolizing genes; nutritional conditions leading to vitamin B(6), B(12), or folate deficiencies; or chronic alcohol consumption. Homocysteine is an intermediate in methionine metabolism, which takes place mainly in the liver. Impaired liver function leads to altered methionine and homocysteine metabolism; however, the molecular basis for such alterations is not completely understood. In addition, the mechanisms behind homocysteine-induced cellular toxicity are not fully defined. In the present work, we have examined the expression of the main enzymes involved in methionine and homocysteine metabolism, along with the plasma levels of methionine and homocysteine, in the liver of 26 cirrhotic patients and 10 control subjects. To gain more insight into the cellular effects of elevated homocysteine levels, we have searched for changes in gene expression induced by this amino acid in cultured human vascular smooth muscle cells. We have observed a marked reduction in the expression of the main genes involved in homocysteine metabolism in liver cirrhosis. In addition, we have identified the tissue inhibitor of metalloproteinases-1 and alpha1(I)procollagen to be upregulated in vascular smooth muscle cells and liver stellate cells exposed to pathological concentrations of homocysteine. Taken together, our observations suggest (1) impaired liver function could be a novel determinant in the development of hyperhomocysteinemia and (2) a role for elevated homocysteine levels in the development of liver fibrosis.
Hypertension 2001 Nov
PMID:Hyperhomocysteinemia in liver cirrhosis: mechanisms and role in vascular and hepatic fibrosis. 1171 26

Hypertension has been implicated as a risk factor for Alzheimer disease (AD) and dementia in epidemiological studies of humans. It is thus possible that there are common genetic determinants for hypertension and AD. Epidemiological, clinical, and experimental data suggest that the renin-angiotensin-aldosterone system is a critical regulator of blood pressure. The presence of an MboI site in an RFLP in the renin gene and the Thr at the Met/Thr polymorphism at codon 235 (M235T) of the angiotensinogen gene have been reported to be associated with hypertension. These variants were studied in autopsy-confirmed AD cases and matched controls from the U.K. While no association was detected with the renin polymorphism, a weak deleterious effect was observed in cases homozygous for the angiotensinogen Thr allele. However, this association was not observed in a French cohort of clinically diagnosed AD cases and controls, suggesting that the initial observation was a type I error. Thus, these polymorphisms are unlikely to be associated with AD risk.
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PMID:Alzheimer disease is not associated with polymorphisms in the angiotensinogen and renin genes. 1180 27

Hyperhomocysteinemia (hHcys) has been recognized as a new risk factor for cardiovascular diseases independent of plasma lipid levels or other factors. However, it remains unknown whether hHcys is implicated in the target organ damages associated with hypertension. The present study first examined the possible role of hHcys in the development of glomerulosclerosis in Dahl salt-sensitive (DS) hypertensive rats. High-performance liquid chromatography showed that plasma total homocysteine (tHcys) concentration was 7.64 +/- 0.29 micromol/L in conscious DS rats on a low salt (0.4% NaCl) diet, which was higher than 5.23 +/- 0.25 micromol/L in Dahl salt-resistant normotensive rats. When these rats were exposed to a high salt (4% NaCl) diet, plasma tHcys markedly increased in DS rats (14.7 +/-1.31 micromol/L) but not in Dahl salt-resistant rats (5.34 +/- 0.54 micromol/L). An iron chelater, desferrioxamine (0.3 mg/kg IV per day), completely normalized high salt--induced elevations of plasma tHcys and significantly attenuated the sclerotic changes in the glomeruli in DS rats. To further determine whether hHcys has an independent effect in the development of glomerulosclerosis, Sprague-Dawley rats were fed drinking water containing methionine (1 g/kg per day) for 6 weeks to produce hHcys. In these rats, plasma tHcys increased to 12.5 +/- 1.9 micromol/L (versus 6.1 +/- 2.6 micromol/L in control rats), and the aorta exhibited typical sclerotic changes, but arterial pressure was not altered. Urinary protein excretion increased to 52 +/- 2 mg/24 hours (versus 17 +/- 2 mg/24 hours in control rats), and the glomerular mesangium was expanded with glomerular hypercellularity, capillary collapse, and fibrous deposition in the rats with hHcys. These results suggest that elevated plasma homocysteine may be an important pathogenic factor for glomerular damage in hypertension independent of arterial pressure.
Hypertension 2002 Feb
PMID:Implications of hyperhomocysteinemia in glomerular sclerosis in hypertension. 1188 87

Dietary and cerebrospinal fluid (CSF) Na(+) may act through brain amiloride-sensitive, Phe-Met-Arg-Phe-NH(2) (FMRFamide)-gated Na(+) channels (FaNaChs) to cause sympathoexcitation and hypertension. We hypothesized that FaNaChs cause sympathoexcitation via the activation of brain "ouabain" and the brain renin-angiotensin system. In conscious Wistar rats, intracerebroventricular (ICV) infusion of Na(+)-rich (0.3 mol/L) artificial CSF (aCSF) and ICV injection of angiotensin II or ouabain increase renal sympathetic nerve activity (RSNA), blood pressure (BP), and heart rate (HR). ICV benzamil, an amiloride analogue, did not affect baseline values and blocked the responses to ICV infusions of Na(+)-rich aCSF but not ICV angiotensin II or ouabain. ICV FMRFamide also increased RSNA, BP, and HR. Blocking brain "ouabain" with ICV antibody Fab fragments abolished the responses to both ICV FMRFamide and Na(+)-rich aCSF. In conscious spontaneously hypertensive rats (SHR) on a high salt intake for 6 weeks, prolonged ICV but not intravenous infusion of benzamil at 10 to 20 microg/h significantly decreased RSNA, BP, and HR in a dose-related manner. The extent of these responses was significantly smaller in SHR on regular salt intake. These findings suggest that benzamil-blockable brain FaNaChs represent the major mechanism through which a small increase in CSF Na(+) by ICV Na(+)-rich aCSF in Wistar rats or high salt intake in SHR initiates sympathoexcitation and hypertension. Enhanced Na(+) entry through FaNaChs appears to activate brain "ouabain" and the brain renin-angiotensin system and, thereby, increases the sympathetic outflow. Brain FaNaChs appear to contribute to the worsening of hypertension in SHR on a high salt diet and, to a small extent, to the maintenance of hypertension in SHR on a regular salt diet.
Hypertension 2002 Feb
PMID:Brain amiloride-sensitive Phe-Met-Arg-Phe-NH(2)--gated Na(+) channels and Na(+)-induced sympathoexcitation and hypertension. 1188 7

ACE inhibitory peptides are biologically active peptides that play a role in blood pressure regulation. When derived from food proteins during food processing or gastrointestinal digestion, these peptides could function as efficient agents in treating and preventing hypertension. However, in order to exert an antihypertensive effect by inhibition of the ACE enzyme, they have to reach the bloodstream intact. The aim of this research was to assess if the known ACE inhibitory peptide Ala-Leu-Pro-Met-His-Ile-Arg, derived from a tryptic digest of beta-lactoglobulin, could be absorbed through a Caco-2 Bbe cell monolayer in an Ussing chamber and reach the serosal side undegraded. Samples of the mucosal compartment showed high ACE inhibitory activity. No or only little ACE inhibitory activity was detected in the serosal compartment. However, when the serosal sample was concentrated three-fold, a substantial ACE inhibitory activity was registered. Concomitantly, HPLC and MS clearly showed the presence of Ala-Leu-Pro-Met-His-Ile-Arg in the mucosal compartment, whereas in the serosal compartment only MS was able to detect the heptapeptide. In conclusion. under the observed experimental conditions, the ACE inhibitory peptide Ala-Leu-Pro-Met-His-Ile-Arg was transported intact through the Caco-2 Bbe monolayer, but in concentrations too low to exert an ACE inhibitory activity.
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PMID:Intestinal transport of the lactokinin Ala-Leu-Pro-Met-His-Ile-Arg through a Caco-2 Bbe monolayer. 1193 86

Epidemiological studies of human populations show that poor growth in utero predisposes an individual to the later development of type 2 (non-insulin-dependent) diabetes mellitus and hypertension in adulthood. This phenomenon is not confined to man; feeding pregnant rats diets moderately deficient in protein has a similar effect, programming the adult blood pressure and glucose metabolism of the offspring. A restriction in the amino acid supply was thought to cause poor fetal growth. However, recent experiments have shown that this is not the case and instead have implicated the metabolism of the S-containing amino acids. Many semi-synthetic experimental diets contain an imbalance in S-containing amino acids, forcing the animal to synthesise a sizeable part of its cysteine requirement from methionine. Unfortunately, when the diet is low in protein, the oxidation of amino acids is reduced, perturbing methionine metabolism and increasing levels of homocysteine. It is this interaction between protein content and composition of the diet which influences neonatal viability and may also determine the long-term health of the offspring. An excess of homocysteine is known to affect levels of two of the main mediators of cellular methylation reactions, S-adenosyl methionine and methylene tetrahydrofolate. S-adenosyl methionine is the methyl donor for the methylation of newly-synthesised DNA, regulating chromatin assembly and gene expression. The balance between S-adenosyl methionine and the methylated derivatives of folic acid may be critical for the development of differentiating cells and the long-term regulation of gene expression.
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PMID:Manipulating the sulfur amino acid content of the early diet and its implications for long-term health. 1200 97

Atrial natriuretic peptides consist of a family of peptide hormones that are synthesized by three separate genes and then stored as three different prohormones (i.e., 126-amino acid [a.a.]) atrial natriuretic peptide (ANP), 108-a.a. brain natriuretic peptide (BNP), and 126-aa. C-natriuretic peptide (CNP) prohormones. The gene encoding for the synthesis of the atrial natriuretic peptide prohormone (proANP) consists of three exons and two introns. Exon 1 encodes the signal peptide and the first 16 aa. of the ANP prohormone. These 16 a.a. form the N-terminus of a peptide hormone named long-acting natriuretic hormone (LANH). A valine-to-methionine substitution in LANH results in a 2-fold increased incidence of strokes in humans. Exon 2 of the proANP gene encodes for three peptide hormones, i.e., vessel dilator, kaliuretic hormone, and ANP. Each of the proANP gene products have vasodilatory, diuretic, natriuretic, and/or kaliuretic properties. Stretch, glucocorticoids, thyroid hormone(s), mineralocorticoids, and calcium enhance proANP gene expression. Enhanced proANP gene expression is found in congestive heart failure, hypertension, and cirrhosis with ascites. The proANP gene is present with invertebrates and plants as well as in humans and other vertebrates.
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PMID:Atrial natriuretic peptide prohormone gene expression: hormones and diseases that upregulate its expression. 1210 71

Several candidate genes, chosen from the renin- angiotensin system, were examined for their association with essential hypertension. The genes of the renin- angiotensin system (RAS) are good candidates for such an approach because this system is well known to be involved in the control of blood pressure. One of these candidate genes is the gene encoding for angiotensinogen (the most important gene of the RAS associated with essential hypertension in the most population, is the gene for angiotensin-converting enzyme- ACE). One DNA polymorphism within exon 2- with threonine instead of methionine at position 235 (M235T) was found to be significantly associated with hypertension. The objective of this study is the analysis of M235T polymorphism in angiotensinogen gene in Romanian patients with essential hypertension as well as controls. We examined 38 patients with essential hypertension and 21 normotensive patients. In order to identify the M235T angioteninogen variant, we used the following methods: DNA extraction, PCR amplification and enzymatic digestion of the PCR product using Tth 111I restriction endonuclease enzyme. In the study groups, the M235T variant (Met?Thr in aminoacid position 235) was found more frequently in hypertensive patients (81,57%), than in control subjects (66,66%). We identified 52,63% M235T heterozygotes in the hypertensive group compared with 47,61% in the control group, and 28,94% T235T homozygotes in the hypertensive group compared with 19,04% in the control group. The results of our study suggest an association of the M235T polymorphism in the gene encoding angiotensinogen with essential hypertension.
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PMID:Essential arterial hypertension and polymorphism of angiotensinogen M235T gene. 1216 9

We studied vascular responses in spontaneously hypertensive rats (SHR) of both genders after methionine (Met) loading to test whether or not there were gender differences. SHRs were divided into 5 groups: male control (MSHR), female control (FSHR), methionine-loaded (+Met) males (MSHR[+Met]) and females (FSHR[+Met]), and male SHR with both 17beta-estradiol (E2) and Met administration (MSHR[+E2+Met]). Treated groups received Met (1g/kg body weight per day) in water for 6 weeks. Systolic blood pressure (SBP) was monitored weekly. Aortic contractile (phenylephrine-induced) and relaxant (acetylcholine-induced as endothelium-dependent relaxation, or EDR) responses as well as endothelial suppression (with nitric oxide synthase inhibitor) were evaluated at the end of experiments. Serum homocysteine (Hcy) level was also determined. Met overloading caused a nearly 3-fold increase in serum Hcy in each gender (moderate hyperhomocysteinemia, or HHcy). As age increased, SBP increased in all groups; FSHR(+Met) had the least elevation and significantly less increase of SBP than FSHR at the end of 6 weeks. There was also a significant increase of EDR in FSHR(+Met) compared with both FSHR and MSHR(+Met). FSHR(+Met) had the highest level of endothelium suppression. Furthermore, EDR in MSHR(+E2+Met) was significantly higher than that in MSHR(+Met). Direct Hcy feeding appeared to reduce the development of hypertension in female SHR in 3 weeks. Hence, SBP development was partially alleviated, whereas EDR and endothelium suppression were enhanced in female SHR with HHcy. E2 could mimic the gender-dependent effect of HHcy on EDR enhancement in MSHR; moreover, reduction of SBP development occurred in Hcy-fed FSHR.
Hypertension 2002 Sep
PMID:Vascular responses in male and female hypertensive rats with hyperhomocysteinemia. 1221 74


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