Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated in a young Italian obese population, the relationship between ambulatory BP (ABP) and several pathophysiological factors linking obesity to hypertension. A total of 89 obese children and adolescents underwent a 24-h ambulatory BP monitoring (ABPM) and an oral glucose tolerance test. The circulating levels of insulin, lipids, uric acid, C-reactive protein, interleukin-6, renin and aldosterone and the 24-h urinary levels of epinephrine, norepinephrine and albumin excretion rate were measured. Nine percent of subjects had daytime sustained hypertension (SH), 26% night-time hypertension and 11% a non-dipping pattern. SH subjects compared to those with sustained normotension (SN) were more obese (P<0.05), with a more frequent family history of hypertension (P<0.05), higher urinary catecholamine (P<0.05) and heart rate values (P<0.05) after adjustment for standard deviation score (SDS) of body mass index (BMI) and sex. Subjects with night-time hypertension compared to those with night-time normotension were more obese (P<0.0001), with a higher prevalence of impaired glucose tolerance (P<0.05) and metabolic syndrome (P<0.05) and higher 2-h glucose (P<0.05), uric acid (P<0.05) and triglycerides (P<0.05). In multivariate regression analysis, daytime systolic BP (SBP) remained independently correlated with urinary norepinephrine and SDS-BMI (P<0.05 for both), daytime diastolic BP (DBP) with waist circumference (P<0.05) and night-time SBP and DBP with SDS-BMI (P<0.01 for both). The risk of having systolic and diastolic hypertension increased with the increase in SDS-BMI and waist circumference, respectively. In conclusion, in our cohort of obese children and adolescents, daytime and night-time hypertension were associated with activation of the sympathoadrenal system and worst metabolic conditions, respectively.
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PMID:Sympathoadrenergic and metabolic factors are involved in ambulatory blood pressure rise in childhood obesity. 1788 27

Adipose tissue inflammation and insulin resistance are central to the pathogenesis of the metabolic syndrome. Spironolactone, an antagonist of mineralocorticoid receptor, glucocorticoid receptor and androgen receptor, and agonist of progesterone receptor, has anti-inflammatory activity. Blockade of the renin-angiotensin-aldosterone system has been shown to improve glucose metabolism. We have investigated whether spironolactone has direct effects on glucose uptake and interleukin-6 secretion in human adipocytes. Spironolactone, but not its active metabolite canrenoic acid, significantly increased basal and insulin-stimulated glucose uptake in cultured IN VITRO-differentiated adipocytes of women, without affecting insulin sensitivity. The effect was not due to changes in abundance of glucose transporters 1 or 4 or in degree of cell differentiation. Spironolactone, but not canrenoic acid, significantly reduced basal interleukin-6 secretion by cultured stromal-vascular cells. These effects of spironolactone were not mediated by ligand-dependent antagonism of the mineralocorticoid, glucocorticoid, or androgen receptors. Spironolactone may have a novel role in increasing glucose uptake into adipose cells and attenuating adipose tissue inflammation, with implications for management of metabolic syndrome.
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PMID:Effects of spironolactone on glucose transport and interleukin-6 secretion in adipose cells of women. 1807 71

Hyperaldosteronism is associated with hypertension, cardiovascular fibrosis, and electrolyte disturbances, including hypomagnesemia. Mechanisms underlying aldosterone-mediated Mg(2+) changes are unclear, but the novel Mg(2+) transporters TRPM6 and TRPM7 may be important. We examined whether aldosterone influences renal TRPM6/7 and the TRPM7 downstream target annexin-1 and tested the hypothesis that Mg(2+) administration ameliorates aldosterone-induced cardiovascular and renal injury and prevents aldosterone-associated hypertension. C57B6 mice were studied (12 weeks, n=8 to 9/group); (1) control group (0.2% dietary Mg(2+)), (2) Mg(2+) group (0.75% dietary Mg(2+)), (3) aldosterone group (Aldo, 400 microg/kg/min and 0.9% NaCl drinking water), and (4) Aldo+Mg(2+) group. Blood pressure was unaltered by aldosterone and was similar in all groups throughout the experiment. Serum Na(+) was increased and serum K(+) and Mg(2+) decreased in the Aldo group. Aldo mice had hypomagnesuria and proteinuria, and renal, cardiac, and aortic fibrosis, which were normalized by Mg(2+) supplementation. Renal and cardiovascular expression of interleukin-6, VCAM1 and COX2 was increased in the Aldo group. Magnesium attenuated renal and cardiac interleukin-6 content and decreased renal VCAM1 and cardiac COX2 expression (P<0.05). Aldosterone decreased expression of renal TRPM7 and the downstream target annexin-1 (P<0.05) without effect on TRPM6. Whereas Mg(2+) increased mRNA expression of TRPM6 and TRPM7, it had no effect on TRPM7 and annexin-1 protein content. Our data demonstrate that aldosterone mediates blood pressure-independent renal and cardiovascular fibrosis and inflammation through Mg(2+)-sensitive pathways. We suggest that altered Mg(2+) metabolism in hyperaldosteronism may relate to TRPM7 downregulation and that Mg(2+) protects against cardiovascular and renal damaging actions of aldosterone.
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PMID:Downregulation of renal TRPM7 and increased inflammation and fibrosis in aldosterone-infused mice: effects of magnesium. 1826 39

Recently, we reported the presence of a local renal aldosterone production. In the present study, we tested the hypothesis that local aldosterone production in the kidney contributes to renal inflammation, matrix formation and albuminuria associated with diabetes. We evaluated changes in renal aldosterone content (RAC), aldosterone synthase expression, nuclear factor kappaB (NFkappaB), tumour necrosis factor alpha (TNFalpha), interleukin-6 (IL-6), transforming growth factor beta (TGFbeta), glomerular fibronectin, collagen type IV and urinary albumin extraction (UAE) in response to the aldosterone synthase inhibitor FAD286. Studies were conducted in adrenalectomized, normoglycaemic (control) or diabetic rats for 14 weeks. The FAD286 was administered during the last 10 weeks of the study. Plasma aldosterone levels were not detectable in any of the study groups. Compared with control rats, diabetic rats had higher levels of RAC by 488% (P < 0.01), NFkappaB by 293% (P < 0.01), TNFalpha by 356% (P < 0.01), IL-6 by 378% (P < 0.01), TGFbeta by 337% (P < 0.01) and UAE by 1122% (P < 0.01), and increased glomerular fibronectin and collagen type IV immunostaining. In diabetic rats, FAD286 reduced RAC (P < 0.01), UAE (P < 0.05), NFkappaB mRNA, TNFalpha mRNA, IL-6 mRNA and TGFbeta mRNA by 51, 41, 41 and 52% and also their proteins and decreased glomerular fibronectin and collagen type IV immunostaining. In conclusion, diabetes increases local aldosterone production in the kidney, which contributes to development of renal inflammation, matrix formation and albuminuria. Inhibition of aldosterone production in the kidney could be helpful in management of diabetic nephropathy.
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PMID:Local renal aldosterone production induces inflammation and matrix formation in kidneys of diabetic rats. 1829 90

Endothelial cells have been shown to induce adrenal steroidogenesis and to enhance aldosterone secretion via angiotensin II and endothelin 1-independent mechanisms. It has been demonstrated that endothelial cells and adrenocortical cells are capable of producing interleukin-6 (IL-6) and IL-6 is a factor known to stimulate adrenal cortisol secretion. We therefore asked whether endothelial cells have an effect on adrenal IL-6 generation and whether IL-6 mediates biosynthesis of aldosterone as is observed after exposure of adrenocortical cells to endothelial cell-conditioned medium (ECCM). Cells from the adrenocortical cancer cell line NCI-H295R were incubated with ECCM produced from human umbilical vein endothelial cells at increasing concentrations. As detected by an enzyme-linked immunosorbent assay, pure ECCM significantly increased IL-6 protein secretion by cultured adrenocortical cells in a dose-dependent fashion, to a 18.0+/-2.0 pg/mL (mean+/-SEM). This was paralleled by an enhanced IL-6 promoter activity as determined with the transfection of an IL-6-promoter-luciferase reporter gene construct. Pure ECCM also induced aldosterone secretion by adrenocortical cells more than three times that of controls with serum-free medium. ECCM PER SE contains significant amounts of IL-6 protein. However, blockade of IL-6 signal transduction did not interfere with aldosterone synthesis. These data suggest that endothelial cells secrete IL-6 and that endothelial cell-derived factors regulate adrenal IL-6 synthesis which does not alter adrenal aldosterone secretion. Our findings support the hypothesis that the endothelium and the adrenal gland may play a role in the development of some forms of hypertension and - more speculative - inflammation.
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PMID:The endothelium secretes interleukin-6 (IL-6) and induces IL-6 and aldosterone generation by adrenocortical cells. 1877 60

Clinical findings suggest that an etiological factor of skin psoriasis (SPs) is of nervous origin. Vasoactive intestinal peptide (VIP) is the most probable candidate for such a factor since VIP is the only neurotransmitter the extracellular level of which increases during SPs exacerbation and decreases in remission. VIP released from skin nerves induces keratinocyte hyperproliferation, angiogenesis, vasodilation, and other SPs-associated cutaneous pathological processes. These can go on over a prolonged period since (1) once released, VIP induces its own further secretion; (2) VIP induces release of interleukin-6 (IL6) that evokes both its own further release and release of VIP. Thereby, a vicious circle-type mechanism perpetuating and amplifying VIP secretion can function in the focuses of psoriatic damage. The mechanism described operates still more intensively under the effects of parathyroid hormone, aldosterone, and enkephalin, the blood levels of which are elevated in patients with SPs. The above explains such features of SPs as its association with human immunodeficiency virus infection, mental stress, alcohol consumption, smoking, and dependence of SPs on skin pigmentation.
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PMID:Self-sustaining pathological processes in skin psoriasis. 1892 42

1. Understanding of the regulatory mechanisms of gene expression in the control of blood pressure and fluid volume is a key issue in cardiovascular medicine. Guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) signalling antagonizes the physiological and pathophysiological effects mediated by the renin-angiotensin-aldosterone system (RAAS) in the regulation of cardiovascular homeostasis. 2. The targeted-disruption of the Npr1 gene (coding for GC-A/PRA) leads to activation of the cardiac RAAS involved in the hypertrophic remodelling process, which influences cardiac size, expression of pro-inflammatory cytokine genes and the behaviour of various hypertrophy marker genes. The Npr1 gene-knockout (Npr1(-/-)) mice exhibit 35-40 mmHg higher systolic blood pressure and a significantly greater heart weight to bodyweight ratio than wild-type (Npr1(+/+)) mice. 3. The expression of both angiotensin-converting enzyme (ACE) and angiotensin II AT(1a) receptors are significantly increased in hearts from Npr1(-/-) mice compared with hearts from Npr1(+/+) mice. In parallel, the expression of interleukin-6 and tumour necrosis factor-alpha is also markedly increased in hearts from Npr1(-/-) mice. 4. These findings indicate that disruption of NPRA/cGMP signalling leads to augmented expression of the cardiac RAAS in conjunction with pro-inflammatory cytokines in Npr1-null mutant mice, which promotes the development of cardiac hypertrophy and remodelling.
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PMID:Regulation of cardiac angiotensin-converting enzyme and angiotensin AT1 receptor gene expression in Npr1 gene-disrupted mice. 1984 97

Adrenomedullin (AM) is located in the zona glomerulosa of the adrenal cortex and is considered to suppress aldosterone release. To determine the effect of AM in primary aldosteronism (PA), we infused AM (2.5 pmol kg(-1) min(-1)) for 27 h, followed by a 15-h recovery period, in a control group (essential hypertensives with plasma aldosterone levels <or=100 pg ml(-1), n=7) and in a PA group (n=5). The control group was also infused with vehicle. Hemodynamic, hormonal, oxidative and inflammatory responses were studied. AM infusion caused similar and steady decreases in blood pressure and several markers for arteriosclerosis (for example, pulse wave velocity) in both groups. Interestingly, AM infusion suppressed aldosterone release to values within the normal range in the PA group (300.0+/-58.4 to 111.6+/-13.5 pg ml(-1), P<0.01). In the control group, aldosterone release suppression was significant but limited (81.7+/-9.1 to 47.9+/-9.9 pg ml(-1), P<0.01). The adrenocorticotropic hormone-cortisol system was not changed by AM infusion. Brain natriuretic peptide was cumulatively increased by prolonged AM infusion in both groups, probably because of cardiac overload. AM did not affect oxidative markers. In addition, a mild but significant increase in C-reactive protein (CRP) mediated by interleukin-6 was observed during AM infusion in every participant, without exception. This pathway might participate in CRP elevation in cardiovascular disease. In summary, AM seems to have an essential role in the suppression of aldosterone release in PA. AM may be an important modulator in PA, and intermediate-term (3 h) AM infusion could be used as an alternative renin-stimulating/aldosterone-suppressing test for PA detection.
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PMID:Aldosterone antisecretagogue and antihypertensive actions of adrenomedullin in patients with primary aldosteronism. 2015 Sep 11

Peroxisome proliferator-activated receptor (PPAR)-gamma modulators, a class of antidiabetic drugs, have been associated with cardiovascular risks in type 2 diabetes in humans. The objective of this study was to explore possible cardiovascular risk biomarkers associated with PPAR-gamma in rodents that could provide an alert for risk to humans. Normal, myocardial infarction-induced heart failure (HF) or Zucker diabetic fatty (ZDF) rats were used. Rats (n = 5-6) were treated with either vehicle or rosiglitazone (RGZ; 3 or 45 mg/kg/day p.o.) for 4 weeks. Biomarkers for potential cardiovascular risks were assessed, including 1) ultrasound for cardiac structure and function; 2) neuroendocrine and hormonal plasma biomarkers of cardiovascular risk; 3) pharmacogenomic profiling of cardiac and renal tissue by targeted tissue low-density gene array representing ion channels and transporters, and components of the renin-angiotensin-aldosterone system; and 4) immunohistochemistry for cardiac fibrosis, hypertrophy, and inflammation (macrophages and tumor necrosis factor-alpha). HF was confirmed by increase in cardiac brain natriuretic peptide expression (p < 0.01) and echocardiography. Adequate exposure of RGZ was confirmed by pharmacokinetics (plasma drug levels) and the pharmacodynamic biomarker adiponectin. In normal or HF rats, RGZ had no negative effects on any of the biomarkers investigated. Similarly, RGZ had no significant effects on gene expression except for the increase in interleukin-6 mRNA expression in the heart and decrease in epithelial sodium channel beta in the kidney. In contrast, echocardiography showed improved cardiac structure and function after RGZ in ZDF rats. Taken together, this study suggests a limited predictive power of these preclinical models in respect to observed clinical adverse effects associated with RGZ.
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PMID:Pharmacogenomic, physiological, and biochemical investigations on safety and efficacy biomarkers associated with the peroxisome proliferator-activated receptor-gamma activator rosiglitazone in rodents: a translational medicine investigation. 2051 51

The ability of the human body to regulate plasma osmolality (POsm) within a very narrow and well defined physiological range underscores the vital importance of preserving water and sodium balance at rest and during exercise. The principle endocrine regulator of whole body fluid homeostasis is the posterior pituitary hormone, arginine vasopressin (AVP). Inappropriate AVP secretion may perpetuate either slow or rapid violation of these biological boundaries, thereby promoting pathophysiology, morbidity and occasional mortality. In the resting state, AVP secretion is primarily regulated by changes in POsm (osmotic regulation). The osmotic regulation of AVP secretion during exercise, however, may possibly be enhanced or overridden by many potential non-osmotic factors concurrently stimulated during physical activity, particularly during competition. The prevalence of these highly volatile non-osmotic AVP stimuli during strenuous or prolonged physical activity may reflect a teleological mechanism to promote water conservation during exercise. However, non-osmotic AVP secretion, combined with high fluid availability plus sustained fluid intake (exceeding fluid output), has been hypothesized to lead to an increase in both the incidence and related deaths from exercise-associated hyponatraemia (EAH) in lay and military populations. Inappropriately, high plasma AVP concentrations ([AVP](p)) associated with low blood sodium concentrations facilitate fluid retention and sodium loss, thereby possibly reconciling both the water intoxication and sodium loss theories of hyponatraemia that are currently under debate. Therefore, given the potential for a variety of exercise-induced non-osmotic stimuli for AVP secretion, hydration strategies must be flexible, individualized and open to change during competitive events to prevent the occurrence of rare, but life-threatening, EAH. This review focuses on the potential osmotic and non-osmotic stimuli to AVP secretion that may affect fluid homeostasis during physical activity. Recent laboratory and field data support: (i) stimulatory effects of exercise intensity and duration on [AVP](p); (ii) possible relationships between changes in POsm with changes in both sweat and urinary osmolality; (iii) alterations in the AVP osmoregulatory set-point by sex steroid hormones; (iv) differences in [AVP](p) in trained versus untrained athletes; and (v) potential inter-relationships between AVP and classical (aldosterone, atrial natriuretic peptide) and non-classical (oxytocin, interleukin-6) endocrine mediators. The review concludes with a hypothesis on how sustained fluid intakes beyond the capacity for fluid loss might possibly facilitate the development of hyponatraemia if exercise-induced non-osmotic stimuli override 'normal' osmotic suppression of AVP when hypo-osmolality exists.
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PMID:Arginine vasopressin, fluid balance and exercise: is exercise-associated hyponatraemia a disorder of arginine vasopressin secretion? 2052 12


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