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)

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.
Hypertension 1999 Jul
PMID:Preactivated peripheral blood monocytes in patients with essential hypertension. 1040 33

The effect of N-acetyl-L-cysteine on interleukin-1beta-induced nitric oxide synthase expression was studied in rat vascular smooth muscle cells to determine if the reduction/oxidation state would modulate cytokine-induced changes. Interleukin-1beta induced the production of nitrite, a stable metabolite of nitric oxide in a time- and dose-dependent manner. Cytokine-induced nitrite production was enhanced by the addition of N-acetyl-L-cysteine in a dose-dependent manner, with a >50% increase produced by the addition of 1 mmol/L N-acetyl-L-cysteine. There was no influence on nitrite production when the cells were treated with N-acetyl-L-cysteine alone. Northern and Western blot analyses revealed that the upregulation of interleukin-1beta-induced nitric oxide production by N-acetyl-L-cysteine resulted from an enhanced expression of inducible nitric oxide synthase. Interferon-gamma or tumor necrosis factor-alpha when used alone had no influence on nitrite production in the absence or presence of N-acetyl-L-cysteine. Nitrite accumulation was higher by the cells treated with interleukin-1beta combined with either interferon-gamma or tumor necrosis factor-alpha compared with those treated with interleukin-1beta alone. N-Acetyl-L-cysteine upregulated nitrite production and inducible nitric oxide synthase expression induced by combination treatment with interleukin-1beta and either interferon-gamma or tumor necrosis factor-alpha. However, N-acetyl-L-cysteine had no significant influence in cytokine-induced activation of nuclear factor-kappaB or signal transducer and activator of transciption-1, as assessed by electrophoretic mobility shift assays. These results demonstrate that N-acetyl-L-cysteine possibly acted as a thiol-containing reducing agent and facilitated the expression of inducible nitric oxide synthase in rat vascular smooth muscle cells by cytokines through a mechanism that is independent of nuclear factor-kappaB or signal transducer and activator of transciption-1.
Hypertension 1999 Oct
PMID:N-acetyl-L-cysteine enhances interleukin-1beta-induced nitric oxide synthase expression. 1052 29

Biophysical forces regulate vascular smooth muscle cell (VSMC) physiology and evoke vascular remodeling. Two VSMC autocrine molecules, insulin-like growth factor I (IGF-I) and nitric oxide (NO), are implicated in remodeling attributable to VSMC hyperplasia. We investigated the role of in vitro cyclic stretch on rat VSMC IGF-I, NO, and cellular growth. Cyclic stretch (1 Hz at 120% resting length for 48 h) stimulated VSMC proliferation 2.5-fold vs. unstretched cells and was accompanied by a 1.8-fold increase in VSMC IGF-I secretion. Despite activation of this proliferative pathway, cyclic stretch induced inducible (i) nitric oxide synthase (NOS) expression and a twofold increase in NO secretion, a molecule with documented antiproliferative effects. Cytokine treatment enhanced iNOS expression and NO secretion while inhibiting vascular growth by approximately 50% in static cells. Cytokine treatment of stretched VSMC enhanced NO secretion 2.5-fold while inhibiting growth by approximately 80%. Exogenous IGF-I increased NOS activity 1.5-fold and NO secretion 8.5-fold in static cells. In turn, iNOS inhibition increased IGF-I secretion 1.6-fold and enhanced VSMC growth 1.6-fold in stretched cells. An NO donor (sodium nitroprusside) similarly inhibited VSMC proliferation in static (24%) and stretched (50%) VSMC while also inhibiting IGF-I secretion from stretched cells by approximately 35%. Thus cyclic stretch stimulates mitogenic (IGF-I) and antimitogenic (NO) pathways in VSMC. These two molecules regulate each other's secretory rates, providing tight regulation of VSMC proliferation. These data may have profound implications in understanding vascular growth alterations in vascular injury and hypertension.
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PMID:Activation of mitogenic and antimitogenic pathways in cyclically stretched arterial smooth muscle. 1170 30

This study was undertaken to review the links between maternal nutrition, offspring's birth weight and the propensity to early insulin resistance and high diabetes rates in Indian adults. Studies included a comparison of maternal size and nutrition with birth weights in Pune, India, and Southampton, UK. In Pune, the growth, insulin resistance and blood pressure of four-year-old children were assessed. Adults >40 years of age, who were resident in rural areas, were compared with adults living in urban areas for size, glucose handling, lipid status and blood pressure. Newly diagnosed diabetic adults living in urban areas were also monitored. Height, weight, head, waist and hip circumferences, skin-fold measurements and blood pressure were routinely measured. Fasting glucose, insulin, total and high-density lipoprotein cholesterol and triglycerides were linked to the glucose and insulin responses during glucose tolerance tests. Cytokine levels were measured in plasma samples of urban and rural adults. Indian babies were lighter, thinner, shorter and had a relatively lower lean tissue mass than the Caucasian babies. However, the subcutaneous fat measurements of these babies were comparable to those of the white Caucasian babies. The Indian mothers were small, but relatively fat mothers produced larger babies. Maternal intake of green vegetables, fruit and milk, and their circulating folate and vitamin C levels, predicted larger fetal size. Rapid childhood growth promoted insulin resistance and higher blood pressure. Rural adults were thin, with a 4% prevalence of diabetes and a 14% prevalence of hypertension, but the risks increased within the normal body mass index (BMI) range. Type 2 diabetes was common in urban adults younger than 35 years of age. Although the average BMI was 23.9 kg m(-2), central obesity and thin limbs were noteworthy. Levels of interleukin-6 and tumour necrosis factor-a were markedly increased in urban dwellers. Hence, there is evidence of a remarkably powerful, intergenerational effect on body size and total and central adiposity. Indians are highly susceptible to insulin resistance and cardiovascular risks, with babies being born small but relatively fat. Insulin resistance is amplified by rapid childhood growth. Dietary factors seem to have profound long-term metabolic influences in pregnancy. Overcrowding with infections and central obesity may amplify cytokine-induced insulin resistance and early diabetes in Indian adults with a low BMI.
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PMID:The lifecycle effects of nutrition and body size on adult adiposity, diabetes and cardiovascular disease. 1216 75

White coat hypertension (WCH) or isolated clinic hypertension is generally accepted to be a benign condition, although some reports have suggested that it may be associated with an increased cardiovascular event rate or other cardiovascular alterations. It has been previously shown that essential hypertension (EH) is associated with abnormalities in haemostatic/fibrinolytic balance and endothelial function. The aim of our study was to assess the impact of WCH on fibrinolytic balance and endothelial function by measuring plasma levels of plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator antigen (tPA), fibrinogen, and thrombomodulin. These markers were determined in 71 patients with EH, 26 with WCH and 87 normotensive healthy control subjects. The three groups were not different with respect to age, gender, smoking habits, BMI and blood lipids. Subjects with WCH were found to have increased plasma levels of PAI-1, tPA, fibrinogen and thrombomodulin compared to controls, but less compared to hypertensive ones. Our results suggest that WCH may be associated with decreased fibrinolytic potential and endothelial dysfunction, indicating that WCH may not be a completely harmless trait.
Eur Cytokine Netw 2006 Jun
PMID:White coat hypertension and haemostatic/fibrinolytic balance disorders. 1684 33

Cardiac remodelling is a key risk factor for the development of heart failure in the chronic phase following myocardial infarction. Our previous studies have shown an anti-remodelling role of ACE2 (angiotensin-converting enzyme 2) in vivo during hypertension and that these protective effects are mediated through increased circulating levels of Ang-(1-7) [angiotensin-(1-7)]. In the present study, we have demonstrated that cardiac myocytes have modest ACE2 activity, whereas cardiac fibroblasts do not exhibit any endogenous activity. As fibroblasts are the major cell type found in an infarct zone following a myocardial infarction, we examined the effects of ACE2 gene delivery to cultured cardiac fibroblasts after acute hypoxic exposure. Cardiac fibroblasts from 5-day-old Sprague-Dawley rat hearts were grown to confluence and transduced with a lentiviral vector containing murine ACE2 cDNA under transcriptional control by the EF1alpha (elongation factor 1alpha) promoter (lenti-ACE2). Transduction of fibroblasts with lenti-ACE2 resulted in a viral dose-dependent increase in ACE2 activity. This was associated with a significant attenuation of both basal and hypoxia/re-oxygenation-induced collagen production by the fibroblasts. Cytokine production, specifically TGFbeta (transforming growth factor beta), by these cells was also significantly attenuated by ACE2 expression. Collectively, these results indicate that: (i) endogenous ACE2 activity is observed in cardiac myocytes, but not in cardiac fibroblasts; (ii) ACE2 overexpression in the cardiac fibroblast attenuates collagen production; and (iii) this prevention is probably mediated by decreased expression of cytokines. We conclude that ACE2 expression, limited to cardiac fibroblasts, may represent a novel paradigm for in vivo therapy following acute ischaemia.
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PMID:ACE2 overexpression inhibits hypoxia-induced collagen production by cardiac fibroblasts. 1760 May 30

We evaluated the hypothesis that a relationship exists between inflammation and the outcome of pharmaceutical cardioversion with amiodarone in recent onset atrial fibrillation. We studied 86 patients with symptomatic recent onset AF and coexisting hypertension and/or chronic stable coronary artery disease. All study participants underwent evaluation with a standardized protocol including echocardiography, cytokine level measurement [interleukin-2 (IL-2), interleukin-6 (IL-6) and high sensitivity C reactive protein (hsCRP)] on admission and at 48h, and administration of intravenous amiodarone. By 48h, 70 patients cardioverted to sinus rhythm. Median serum IL-2 levels on admission were higher in non-cardioverted compared to cardioverted patients (P=0.002). At 48h, non-cardioverted had significantly higher IL-6 (P=0.005) and hsCRP values (P=0.001) compared to cardioverted. Multivariate logistic regression analysis showed that lower IL-2 admission levels were a powerful independent predictor for successful cardioversion (OR: 0.154, 95% CI: 0.043-0.552, P=0.004). In patients with hypertension and/or chronic stable coronary artery disease and symptomatic recent onset AF, low serum IL-2 levels on admission are associated with successful cardioversion with amiodarone. This observation highlights the role of inflammation in AF and might have further prognostic and therapeutic implications.
Cytokine 2007 Dec
PMID:Interleukin-2 serum levels variations in recent onset atrial fibrillation are related with cardioversion outcome. 1792 14

The vascular inflammatory response involves complex interaction between inflammatory cells (neutrophils, lymphocytes, monocytes, macrophages), endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and extracellular matrix (ECM). Vascular injury is associated with increased expression of adhesion molecules by ECs and recruitment of inflammatory cells, growth factors, and cytokines, with consequent effects on ECs, VSMCs and ECM. Cytokines include tumor necrosis factors, interleukins, lymphokines, monokines, interferons, colony stimulating factors, and transforming growth factors. Cytokines are produced by macrophages, T-cells and monocytes, as well as platelets, ECs and VSMCs. Circulating cytokines interact with specific receptors on various cell types and activate JAK-STAT, NF-kappaB, and Smad signaling pathways leading to an inflammatory response involving cell adhesion, permeability and apoptosis. Cytokines also interact with mitochondria to increase the production of reactive oxygen species. Cytokine-induced activation of these pathways in ECs modifies the production/activity of vasodilatory mediators such as nitric oxide, prostacyclin, endothelium-derived hyperpolarizing factor, and bradykinin, as well as vasoconstrictive mediators such as endothelin and angiotensin II. Cytokines interact with VSMCs to activate Ca(2+), protein kinase C, Rho-kinase, and MAPK pathways, which promote cell growth and migration, and VSM reactivity. Cytokines also interact with integrins and matrix metalloproteinases (MMPs) and modify ECM composition. Persistent increases in cytokines are associated with vascular dysfunction and vascular disease such as atherosclerosis, abdominal aortic aneurysm, varicose veins and hypertension. Genetic and pharmacological tools to decrease the production of cytokines or to diminish their effects using cytokine antagonists could provide new approaches in the management of inflammatory vascular disease.
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PMID:Inflammatory cytokines in vascular dysfunction and vascular disease. 1941 99

Patients with hypertension have higher mortality rates from hemorrhagic shock (HS) than normotensive patients. Several inflammatory mediators such as tumor necrosis factor alpha (TNF-alpha) and interleukin 10 (IL-10) can be produced by HS and lead to multiple organ dysfunction and death. We investigated the effects of high dose (10 mg/kg/hr) and low dose (1 mg/kg/hr) propofol treatment after HS in conscious spontaneously hypertensive rats (SHRs). By withdrawing 40% of total blood volume from a femoral arterial catheter (6 ml/100 g body weight [BW]) for more than 30 min, HS was induced. The mean arterial pressure (MAP) and heart rate (HR) were monitored continuously for 24 hr after the start of blood withdrawal. Levels of biochemical parameters, including glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), blood urea nitrogen (BUN), creatinine (Cre), creatine phosphokinase (CPK), and lactic dehydrogenase (LDH) were measured 30 min before and 0, 1, 3, 6, 9, 12, 18, and 24 hr after the 30-min blood withdrawal period. Cytokine levels, including TNF-alpha and IL-10 in the serum, were measured 1 hr after HS. The kidney, liver, and lung were removed for pathology assessment at 48 hr after HS. HS significantly increased blood GOT, GPT, BUN, LDH, CPK, TNF-alpha, and IL-10 levels in conscious SHRs. Posttreatment propofol decreased serum TNF-alpha level, increased serum IL-10 level, attenuated the severity of organ damage, and improved survival rate after HS. This treatment protected SHRs against HS-induced organ damage. Moreover, high-dose propofol had a more protective effect than low-dose propofol against HS in conscious SHRs.
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PMID:Propofol protects against hemorrhagic shock-induced organ damage in conscious spontaneously hypertensive rats. 1941 78

Bone morphogenetic proteins (BMPs) are multifunctional growth factors belonging to the transforming growth factor beta (TGFbeta) superfamily. Recent observations clearly emphasize the emerging role of BMPs in angiogenesis: (i) two genetic vascular diseases (hereditary hemorrhagic telangiectasia (HHT) and pulmonary arterial hypertension (PAH)) are caused by mutations in genes encoding components of the BMP signalling pathway (endoglin, ALK1 and BMPRII). (ii) BMP9 has been identified as the physiological ligand of the endothelial receptor ALK1 in association with BMPRII. This review will focus on the diverse functions of BMPs in angiogenesis. We will propose a model that distinguishes the BMP2, BMP7 and GDF5 subgroups from the BMP9 subgroup on the basis of their functional implication in the two phases of angiogenesis (activation and maturation).
Cytokine Growth Factor Rev 2009 Jun
PMID:Emerging role of bone morphogenetic proteins in angiogenesis. 1950 96


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