Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. This randomised, placebo-controlled, double-blind, parallel-group study was conducted to assess the effect of tenidap sodium 120 mg, a novel anti-arthritic cytokine modulating drug, on the hypotensive efficacy of the thiazide diuretics hydrochlorothiazide or bendrofluazide. 2. Twenty-three male and female patients, aged 41-78 years, with mild to moderate, uncomplicated, essential hypertension controlled with thiazide diuretic therapy, received either a single daily dose of tenidap sodium 120 mg or matched placebo for 22 days in addition to their diuretic therapy. Changes between baseline and endpoint in supine and standing systolic and diastolic pressures and pulse rate were compared between treatment groups. 3. Daily treatment with tenidap reduced the anti-hypertensive efficacy of the thiazide diuretics. Blood pressure tended to increase marginally and the increase in mean standing diastolic pressure observed with tenidap was significantly greater than the change in the placebo group. All pressures tended to decrease in the placebo group and all endpoint measurements were within 7 mm Hg of baseline in both groups. 4. Treatment-related side effects of mild to moderate severity were reported in two subjects receiving tenidap, but in neither case was treatment discontinued. Two subjects receiving placebo also experienced side effects considered to be treatment-related and both were withdrawn from the study. 5. The results of this study suggest that tenidap may be given to patients treated for mild to moderate essential hypertension controlled with thiazide therapy; however, the patient's blood pressure should be regularly monitored.
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PMID:The effect of tenidap on the anti-hypertensive efficacy of thiazide diuretics in patients treated for mild to moderate hypertension. 754 96

1. A randomised, placebo controlled, double-blind, parallel group study was conducted to assess the effect of tenidap sodium, a novel cytokine modulating drug, on the stable hypotensive response to the angiotension converting enzyme (ACE) inhibitor enalapril in subjects with mild to moderate, uncomplicated, essential hypertension. 2. Twenty-four male and female hypertensives, aged 33-77 years, received either 120 mg tenidap sodium or matched placebo daily for 22 days concomitantly with enalapril. 3. Mean endpoint supine and standing, systolic and diastolic pressures remained within 10% of baseline in each treatment group. However, the endpoint values were marginally above baseline during double-blind treatment with tenidap and marginally below baseline in the group receiving placebo. The increases in supine and standing systolic pressures in the tenidap group differed significantly from the changes in the placebo group. There were no significant differences between groups in changes in pulse rate. 4. Gastrointestinal side effects of mild to moderate severity attributed to treatment with tenidap were experienced by five subjects, one of whom was withdrawn during the third week of treatment. One subject receiving placebo was withdrawn because of a moderate headache attributed to study treatment. 5. The results of this study suggest that treatment with tenidap may interfere with the anti-hypertensive efficacy of ACE inhibitors. It is recommended that blood pressure should be monitored when tenidap is administered concomitantly with an ACE inhibitor.
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PMID:The effect of tenidap on the anti-hypertensive efficacy of ACE inhibitors in patients treated for mild to moderate hypertension. 754 97

The dysfunction of the immune system has been implicated in the cause of essential hypertension (EH). On the other hand, interleukin- 1beta (IL-1beta) has strongly been involved in the pathogenesis of atheromatosis, whereas our preliminary experiments in serum samples from hypertensive patients before any drug therapy have shown the presence of high concentrations of IL-1beta and the absence of interleukin-2 (IL-2). The aim of this study was first to confirm our preliminary findings and second to investigate the possible interrelation(s) among the parameters studied, particularly between the immunologic markers and the blood pressure or the lipid parameters, because so far there are no data regarding the possible participation of IL-1beta in the cascade phenomena presented during the process of EH such as atherogenesis. Serum samples from 28 consecutive unselected patients with EH before any drug administration or after discontinuation of the antihypertensive therapy for at least 4 weeks, 31 normotensive patients with familial hypercholesterolemia (FH, disease control group), and 35 healthy individuals In a control group matched for age and sex were investigated for the presence of IL-1beta (commercial enzyme immunoassay), soluble IL-2 receptors (slL-2Rs, sandwich enzyme-linked immunosorbent assay set up in our laboratory), and some of the acute phase proteins by nephelometry. In addition, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoproteins A1 and B, and lipoprotein (a) were determined by standard methods. The data were analyzed by unpaired t test, Mann Whitney-U, chi-squared analysis after Yate's correction, analysis of variance, or Kruskal-Wallis where applicable. Correlation coefficient was calculated by simple regression analysis (r) or nonparametric Spearman correlation coefficient (rs). We found that (1) none of the patients had increased concentrations of sIL-2Rs, and (2) the IL-1beta levels significantly differed in the three groups (p = 0.0001). In more detail, the concentrations of IL-1beta were significantly higher in patients with EH compared with those in patients with FH (p < 0.0005) and the healthy control group (p = 0.0001). By contrast, the IL-1beta concentrations did not differ between patients with FH and the healthy control group. (3) Sixteen (57.1%) patients with EH and only 6 (19.4%) patients with FH (p < 0.01) had increased levels of IL-1beta, and (4) the IL-1beta was not correlated with the acute phase reactants or the lipid parameters in the groups studied. However, the group of patients with EH and increased IL-1beta levels had significantly higher mean concentrations of triglycerides (p < 0.05) and significantly lower mean concentrations of high-density lipoprotein cholesterol (p < 0.05) than those who had IL-1beta levels lower than the cutoff point. (5) The IL-1beta concentrations were positively though slightly correlated with the mean blood pressure only in the group of patients with EH (r = 0.38, p < 0.05). This study demonstrated the presence of high concentrations of IL-1beta and the absence of indicators of cellular immune activation in the systemic circulation of patients with EH, suggesting that this cytokine may be involved in the pathogenesis of EH. In addition, this study showed that the high levels of IL-1beta were associated with lipid indicators of atheromatosis only in the group of patients with EH. More studies are required in an attempt to address whether IL-1beta could have a pathogenetic importance in EH. Taking into account these findings, however, it can be suggested that the presence of high IL-1beta levels may be an additional and perhaps independent risk factor for atheromatosis in patients with EH.
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PMID:Increased serum levels of interleukin-1beta in the systemic circulation of patients with essential hypertension: additional risk factor for atherogenesis in hypertensive patients? 904 11

The balance between pro- and anti-inflammatory cytokines has been implicated in the pathogenesis of infectious and auto-immune diseases, and its modulation has been proposed as a potential therapeutic target. The results reported in the present study show that modulators of the renin-angiotensin system, such as the angiotensin-converting enzyme (ACE)-inhibitor captopril and the angiotensin II receptor type I antagonist valsartan, have potent inhibitory effects on the lipopolysaccharide (LPS)-stimulated production of pro-inflammatory cytokines tumour necrosis factor (TNF) and interleukin-1 (IL-1) in vitro. The anti-inflammatory cytokine IL-1Ra is increased by captopril, whereas IL-6 production is decreased by valsartan. These effects are exerted mainly at high concentrations of the drugs. Administration of one dose of captopril or valsartan in therapeutic dosages to patients with essential hypertension did not influence LPS-stimulated production of cytokines by whole blood. In conclusion, despite inhibitory effects on pro-inflammatory cytokine production in vitro, it is unlikely that captopril or valsartan could be used in anticytokine therapeutic strategies in vivo.
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PMID:The effect of renin-angiotensin system inhibitors on pro- and anti-inflammatory cytokine production. 976 20

The immune maladaptation hypothesis of preeclampsia is concordant with cytokine-mediated oxidative stress, chronology of endothelial activation, lipid changes, adverse effect of changing partners, and the protective effect of sperm exposure. Genetic factors may involve underlying hereditary thrombophilic disorders and hyperhomocysteinemia, essential hypertension and/or obesity, or control of the Th1/Th2 balance and thus affect the maternal response against fetal antigens. Placental ischemia and increased syncytiotrophoblast deportation are probably end-stage disease phenomena.
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PMID:The immunology of preeclampsia. 1010 68

The purpose of this study was to investigate the possible involvement of human peripheral blood monocytes in the pathology of hypertensive disease. We determined the in vitro secretion patterns of proinflammatory cytokines obtained from isolated peripheral monocytes from normal controls and from hypertensive patients either after in vitro stimulation with angiotensin II (Ang II) with or without preincubation with an Ang II type 1 receptor antagonist (losartan) or after stimulation with lipopolysaccharide. Blood samples were obtained from 22 patients with essential hypertension (before any drug administration or after interruption of antihypertensive therapy) and from 24 normotensive healthy individuals used as a control group. Peripheral blood monocytes were isolated by density gradient centrifugation and plastic adherence. The state of monocyte activity was determined by the capacity to secrete tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6, (IL-6) either spontaneously or after stimulation. Cytokine concentrations were determined in culture supernatants by specific ELISA. Proinflammatory cytokine levels were assessed by semiquantitative reverse transcribed polymerase chain reaction. After stimulation with Ang II, the IL-1beta secretion of peripheral blood monocytes was significantly increased in hypertensive patients versus healthy individuals (P<0.05). In contrast, in monocytes preincubated with losartan before exposure to Ang II, IL-1beta secretion was diminished in both groups to comparable levels. The secretion of IL-1beta and TNF-alpha was significantly increased in peripheral blood monocytes from hypertensive patients versus healthy individuals after stimulation with lipopolysaccharide (TNF-alpha, P<0.02; IL-1beta, P<0.05). Upregulation of IL-1beta and TNF-alpha secretion in peripheral blood monocytes from hypertensive patients was also seen at the RNA level. Our results indicate preactivated peripheral blood monocytes in hypertensive patients. Ang II may be directly involved in the process of monocyte activation.
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PMID:Preactivated peripheral blood monocytes in patients with essential hypertension. 1040 33

Low rates of coronary heart disease was found in Greenland Eskimos and Japanese who are exposed to a diet rich in fish oil. Suggested mechanisms for this cardio-protective effect focused on the effects of n-3 fatty acids on eicosanoid metabolism, inflammation, beta oxidation, endothelial dysfunction, cytokine growth factors, and gene expression of adhesion molecules; But, none of these mechanisms could adequately explain the beneficial actions of n-3 fatty acids. One attractive suggestion is a direct cardiac effect of n-3 fatty acids on arrhythmogenesis. N-3 fatty acids can modify Na+ channels by directly binding to the channel proteins and thus, prevent ischemia-induced ventricular fibrillation and sudden cardiac death. Though this is an attractive explanation, there could be other actions as well. N-3 fatty acids can inhibit the synthesis and release of pro-inflammatory cytokines such as tumor necrosis factoralpha (TNFalpha) and interleukin-1 (IL-1) and IL-2 that are released during the early course of ischemic heart disease. These cytokines decrease myocardial contractility and induce myocardial damage, enhance the production of free radicals, which can also suppress myocardial function. Further, n-3 fatty acids can increase parasympathetic tone leading to an increase in heart rate variability and thus, protect the myocardium against ventricular arrhythmias. Increased parasympathetic tone and acetylcholine, the principle vagal neurotransmitter, significantly attenuate the release of TNF, IL-1beta, IL-6 and IL-18. Exercise enhances parasympathetic tone, and the production of anti-inflammatory cytokine IL-10 which may explain the beneficial action of exercise in the prevention of cardiovascular diseases and diabetes mellitus. TNFalpha has neurotoxic actions, where as n-3 fatty acids are potent neuroprotectors and brain is rich in these fatty acids. Based on this, it is suggested that the principle mechanism of cardioprotective and neuroprotective action(s) of n-3 fatty acids can be due to the suppression of TNFalpha and IL synthesis and release, modulation of hypothalamic-pituitary-adrenal anti-inflammatory responses, and an increase in acetylcholine release, the vagal neurotransmitter. Thus, there appears to be a close interaction between the central nervous system, endocrine organs, cytokines, exercise, and dietary n-3 fatty acids. This may explain why these fatty acids could be of benefit in the management of conditions such as septicemia and septic shock, Alzheimer's disease, Parkinson's disease, inflammatory bowel diseases, diabetes mellitus, essential hypertension and atherosclerosis.
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PMID:Beneficial effect(s) of n-3 fatty acids in cardiovascular diseases: but, why and how? 1113 72

With a view to evaluating the putative involvement of cytokine gene variants in human essential hypertension, we carried out an association (case-control) study on 174 unrelated nationals (81 hypertensives and 93 normotensives) from the Abu Dhabi Emirate (UAE), a genetically homogeneous population also characterised by the absence of traditional confounding factors such as alcohol consumption and smoking. To that end, we targeted our investigation to five candidate gene loci-transforming growth factor beta1 (TGF-beta1), interferon gamma (IFN-gamma), epidermal growth factor (EGF), interleukin-1 beta (IL-1beta) and tumour-necrosis factor (TNF-alpha) genes. We investigated the distribution of genotypes and alleles of the six following dimorphic variants: TGF-beta1(*)10(T>C) and TGF-beta1(*)25(G>C), located at codons 10 and 25, respectively, of TGF-beta1; T874A in intron 1 of IFN-gamma; G61A in exon 1 of EGF; TaqI dimorphism at +3962 (exon 5) of IL-1beta; and -308A>G in the promoter of TNF-alpha. These six bi-allelic markers were visualised by methods based on the techniques of amplification refractory mutation system-polymerase chain reaction (for TGF-beta1, IFN-gamma, EGF and TNF-alpha) and by polymerase chain reaction-TaqI restriction endonuclease analysis in the case of IL-1beta. In each of the two groups (normotensives and hypertensives), genotype frequencies of all six markers occurred in Hardy-Weinberg proportions. There were, however, no statistical differences in the allele and genotype frequencies of any of the six markers between the two groups of subjects: TGF-beta1(*)10C frequencies were 0.46 and 0.49 (chi(2)=0.61; 2 d.f.; P=0.74) and TGF-beta1(*)25C were 0.07 and 0.08 (chi(2)=0.61; 2 d.f.; P=0.74) amongst normotensives and hypertensives, respectively; p(IFN-gamma(*)A874) were 0.41 in normotensives versus 0.46 in hypertensives (chi(2)=3.07; 2 d.f.; P=0.22); p(EGF (*)G61) were 0.51 versus 0.58 (chi(2)=1.76; 2 d.f.; P=0.41); p[IL-1beta (*)TaqI(+)] were 0.43 versus 0.36 (chi(2)=2.08; 2 d.f.; P=0.35); and p(TNF-alpha(*)-308G) were 0.80 versus 0.85 (chi(2)=1.29; 2 d.f.; P=0.53). There was also no difference in distribution and frequencies of haplotypes constructed with combinations of TGF-beta1(*)10(T>C) and TGF-beta1(*)25(G>C) sites. However, although they do not reach statistical significance (which may be due to the relatively restricted number of subjects included in this study), the distribution differences (in normotensives and hypertensives) observed in the cases of EGF and TNF-alpha reflect trends that could be expected from a mechanistic explanation of the pathways that underlie the patho-physiology of hypertension.
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PMID:A study of five human cytokine genes in human essential hypertension. 1200 75

Several studies have proposed a relationship between blood pressure and inflammation. Interleukin-6 (IL-6) is a multifunctional cytokine involved in inflammation and tissue injury and potentially influencing blood pressure. Recently, a common polymorphism of the IL-6 gene, associated with differences in the transcription rate of the protein, has been described. The aim of this study was to investigate a possible association between genetic variations of the -174GC polymorphism of the IL-6 gene promoter and hypertension in humans. IL-6 gene promoter polymorphism was evaluated by polymerase chain reaction followed by restriction enzyme analysis in 210 elderly Italian patients affected by essential hypertension (EH) and 177 age- and sex-matched controls. The distribution of IL-6 genotypes was 85 GG, 88 GC, 37 CC in the hypertensive patients and 65 GG, 73 GC, 39 CC in the control subjects. In this elderly cohort, no statistically significant association was found between the two groups (P = 0.45 for GG homozygous, P = 0.89 for GC heterozygous and P = 0.27 for CC homozygous). In conclusion the -174 GC polymorphism of the IL-6 gene promoter is not a marker for EH in this sample of elderly Italians.
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PMID:The -174 G/C polymorphism of the interleukin-6 gene promoter and essential hypertension in an elderly Italian population. 1221 60

This study is to explore the association between M235T allele polymorphism of angiotensinogen (AGT) gene and cytokines using essential hypertension probands research method. In hypertensives and controls, polymerase chain reaction combined with restriction endonuclease digestion was used to detect the target genotype variation, and enzyme-lined immunosorbant assay (ELISA) was used to detect the cytokine concentrations (IL-1, IL-6, TNF). The results showed that in hypertensives AGT gene, TT genotype was 55.88%, MT 35.29% and MM 8.82%. The ratio of T/M allele frequency was 0.735/0.265. In controls AGT gene, TT genotype was 47.46%, MT 42.37% and MM 10.17%. The ratio of T/M allele frequency was 0.686/0.314. AGT gene 235 T allele frequency in hypertensives was slightly higher than those in controls. Furthermore AGT gene 235 TT genotype and T allele frequency in middle and high grade of hypertensives were significantly higher than those in mild grade. In subjects of AGT 235 T allele group, the concentrations of IL-1, IL-6 and TNF in hypertensives were significantly higher than those in controls. In subjects of AGT gene 235 M allele frequency, the concentrations of IL-1 and IL-6 in hypertensives were no significant than those in controls. No matter in groups more than 60 years old or less than 60 years old, the concentrations of IL-1, IL-6 and TNF in hypertensives were higher than those in controls. No matter in hypertensives or controls, there were no differences in concentrations of IL-1, IL-6 and TNF when comparing groups more than 60 years old with groups less than 60 years old. The study indicated that AGT gene TT genotype and AGT gene 235 T allele frequency may be an important risk factor for hypertension. The high frequency of AGT gene 235 T allele and the high concentrations of IL-1, IL-6 and TNF in hypertensives may cause hypertension developing. It is also suggested the cytokines may effect the transcription and expression of AGT gene 235 TT genotype in hypertension. The concentrations of IL-1, IL-6 and TNF had nothing to do with age no matter hypertensives or controls.
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PMID:[Studies of the association between angiotensinogen gene regulation and cytokines in essential hypertension]. 1466 17


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