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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Osteopontin (OPN), a proinflammatory cytokine, plays an important role in renal fibrosis. We reported that plasma OPN levels were higher in patients with primary aldosteronism than with essential hypertension. However, the regulatory mechanism of OPN by aldosterone remains unclear. Here, we report the transcriptional regulation of OPN expression by aldosterone and the functional effects of aldosterone-mediated OPN transcription in renal fibroblasts. Aldosterone induced OPN expression in a dose-dependent manner with significant responses at 10 nmol/L (1.6+/-0.2-fold of controls, P<0.05, n=5) and elicited maximal effects at 10 micromol/L (3.5+/-0.4-fold of controls, P<0.01, n=5). Aldosterone increased OPN expression in a time-dependent manner with a maximal effect after 48 hours (2.7+/-0.3-fold of controls, P<0.01, n=5). This effect was abolished by the mineralocorticoid receptor (MR) antagonist spironolactone. Luciferase promoter deletion assays identified a novel cis regulatory element (-2153 to -1758) in the OPN promoter that is responsive to aldosterone. This element contains an activator protein-1 (AP-1) and nuclear factor kappa B (NF kappaB) site. Electrophoretic mobility shift assays, supershift assays, and chromatin immunoprecipitation assays identified both AP-1 and NF kappaB as the DNA binding proteins induced by aldosterone with spironolactone inhibiting aldosterone-induced AP-1 or NF kappaB activity. OPN-siRNA inhibited completely the induction of cell proliferation, type I, III, and IV collagen synthesis by aldosterone. These results indicate that aldosterone induced MR-mediated OPN expression through AP-1 and NF kappaB activation and suggest that aldosterone plays an important role in renal fibrosis through the induction of OPN.
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PMID:Osteopontin in rat renal fibroblasts: functional properties and transcriptional regulation by aldosterone. 1815 41

In this study, the protective effect of extract of Hsian-tsao (Mesona procumbens) (EHT) against liver fibrogenesis in carbon tetrachloride (CCl(4))-injured rats was evaluated. The inhibitory effect of oleanolic acid (OA) and ursolic acid (UA), which are the active compounds in EHT, on the activation of hepatic stellate cells (HSC) was also determined. The results showed that EHT at a dosage of 1.2g/kg of b.w. significantly reduced the liver injury induced by CCl(4) in rats. It also decreased the activity of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and the deposition of collagen in the liver. Oral administration of EHT reduced the levels of alpha-smooth muscle actin (alpha-SMA) and the activity of metalloproteinases (MMPs) in rats injured by treatment with CCl(4). In addition, we performed experiments with the rat hepatic stellate cell line HSC-T6 in which we induced the expression of MMP-2 and alpha-SMA with phorbol-12-myristate-13-acetate (PMA). Treating these cells with OA (20microM) or UA (10microM) caused a decrease in the levels of both proteins. Taken together, our data indicate that EHT can efficiently inhibit CCl(4)-induced liver fibrosis in rats. EHT may therefore be a useful functional food for preventing liver fibrosis.
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PMID:Hsian-tsao (Mesona procumbens Heml.) prevents against rat liver fibrosis induced by CCl(4) via inhibition of hepatic stellate cells activation. 1892 13

Catecholamines due to various mechanisms may contribute to the accumulation of collagen fibers and extracellular matrix in the arterial wall. The aim of this study was to compare intima-media thickness (IMT) of the common carotid artery (CCA) and carotid bifurcation (CB) in patients with pheochromocytoma, essential hypertension and healthy controls. Carotid ultrasound studies were carried out in 30 patients with pheochromocytoma matched for age and gender with 80 patients with essential hypertension and 40 normotensive controls. Significantly higher IMT was found in patients with pheochromocytoma and essential hypertension compared to controls when measured in the CCA (0.931+/-0.223, 0.825+/-0.146 and 0.738+/-0.113 mm; P<0.001; P<0.05), and only in patients with pheochromocytoma compared to controls in the region of CB (1.359+/-0.593, 1.095+/-0.311 and 0.968+/-0.247 mm; P<0.001; P=0.13). Higher IMT in patients with pheochromocytoma compared to patients with essential hypertension was also statistically significant in both carotid regions (both P<0.01). This difference remained significant after adjustment for all relevant clinical and biochemical covariates in the CCA (P=0.014) but disappeared in the region of CB (P=0.079). In summary, patients with pheochromocytoma have increased common carotid IMT when compared to patients with essential hypertension. This finding could be caused by the deleterious effects of the excess of catecholamines on the vascular wall growth and thickening.
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PMID:Increased carotid intima-media thickness in patients with pheochromocytoma in comparison to essential hypertension. 1897 41

The elasticity of a given arterial segment of the aorta and of big elastic arteries is not constant but depends on its distending pressure. As distending pressure increases, there is greater recruitment of inelastic collagen fibers and thereby a reduction in elasticity. It also depends on structural changes in the medial layer of the elastic arteries (mainly aorta and major arterial conduits), and is largely the result of progressive elastic fibre degeneration.Aortic Pulse Wave Velocity (PWV), is the most robust marker of arterial stiffness, however additional useful information can also be provided by the Central Augmentation Index (AIx C), and pulse pressure. The presence of systemic inflammation in cardiovascular disease and in particular in essential hypertension affects arterial stiffness and increases PWV. Some pharmacological and non-pharmacological interventions may improve arterial stiffness and thereby decrease PWV.
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PMID:The pathogenesis of arterial stiffness and its prognostic value in essential hypertension and cardiovascular diseases. 1956 73

Essential hypertension (HTA) is a multifactorial disease and in Chile, its prevalence is 33.7%. There is a genetic predisposition to develop hypertension, whose magnitude is approximately 30 to 50%. At present, some factors are known to increase the risk for cardiovascular disease, but widely accepted biomarkers for screening are missing. The first studies that looked for candidate genes have focused on the renin-angiotensin--aldosterone, aducina, adrenoreceptors beta, G protein subunits, G protein signaling regulators, kinases associated with G proteins and Rho kinases. Studies of DNA sequencing search for polymorphisms and variants through single nucleotide polymorphisms, have been used to seek partnerships with complex or multifactorial diseases, like HTA. Examples of these are: components of collagen proteins, genes related to cell myocardial proteins belonging to cytochrome P450 and growth factors, among others. It is still unlikely to count in a near future with a universal marker. Most probably, a series of markers that confer susceptibility to a specific individual will have to be used in prevention programs or personalized therapy.
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PMID:[Genetic markers in essential hypertension]. 2091 89

Purpose. This study was undertaken to examine adverse changes in coronary hemodynamics associated with hypertension, aging, and excessive salt intake. To dissociate from the possible effects of atherosclerosis, the study was done in rats because they do not develop atherosclerosis. Moreover, this strain of spontaneously hypertensive rats (SHR) develops hypertension similar to essential hypertension in man.Methods. Systemic and coronary hemodynamics, left ventricular mass, and collagen content in normotensive and SHR of various ages and given different treatments were determined.Results. Compared with normotensive Wistar-Kyoto rats, coronary blood flow reserve was lower and minimal coronary vascular resistance was higher in SHR of all ages; an age-related decrease in flow reserve and an increase in minimal vascular resistance were observed for both strains of rats. In very old rats with isolated systolic hypertension, an increase in left ventricular collagen was associated with coronary insufficiency; antihypertensive therapy nearly normalized both measures. In SHR excessive salt intake increased pressure, increased collagen deposition in myocardial interstitium and perivascularly, and impaired coronary circulation; angiotensin II receptor blocker therapy prevented fibrosis and improved coronary hemodynamics.Conclusion. In conclusion, these data indicate that considerable coronary insufficiency associated with hypertension, aging, and salt overload exists in the absence of atherosclerotic coronary changes. Perivascular fibrosis within myocardium may significantly contribute to the coronary vascular impairment.
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PMID:Coronary circulation in hypertension and aging: an experimental study. 2160 50

In physiological, as well as pathological situations, aldosterone significantly influences volume, pressure and electrolyte balance. Primary hyperaldosteronism is caused by autonomous over-production, most frequently due to adrenal adenoma. Patients with primary hyperaldosteronism (Conn's syndrome) have more pronounced left ventricular hypertrophy and higher frequency of cardiovascular events than patients with essential hypertension (EH) with comparable blood pressure values. Consequently, there is an increased interest in the role ofaldosterone tissue function in cardiovascular disease. The aim of the present paper is to emphasise the pleiotropic actions of aldosterone on cardiovascular system and the options for their therapeutic management. Apart from the effects of circulating aldosterone on BP and its renal actions on water and electrolyte excretion, extra-renal effects are also been explored; paracrine affects through tissue mineralocorticoid receptors (MR) may impact on endothelial dysfunction, vascular elasticity, inflammatory changes in the myocardium, vessels and kidneys. Initial oxidative stress due to increased aldosterone concentrations may initiate subclinical endothelial changes and subsequent myocardial fibrosis. The effects on all three layers of vascular wall, together with increased blood coagulation and vascular thrombogenicity increases likelihood of microthrombosis and tissue microinfarctions. Slight increase in aldosterone concentrations in cardiac tissue adversely affects myofibrils as well as coronary artery function. Similar to peripheral vessels, it increases collagen content and changes vascular rigidity and the velocity of pulse wave and facilitates development of perivascular fibrosis. Higher salt intake may potentiate these pathophysiological effects of aldosterone, while higher intake of potassium may restrict them. Aldosterone vasculopathy together with perivascular fibrosis occurring at aldosterone concentrations seen with heart failure contributes to manifestation of heart failure. Consequently, aldosterone may rightly be called "cardiovascular toxin". The adverse effects of aldosterone in patients on long-term ACEI therapy are further facilitated by the aldosterone's ability to evade inhibitory effects of ACEI and parallel activation of renin-angiotensin system. To manage these situations, receptors of mineralcorticoids or direct renin inhibitor aliskiren are used. The positive effect of MR blockade is based on an increased release of nitric oxide (NO) with further improvement in endothelial functions. Detailed review of pleotropic effects of aldosterone helps to clarify a number of pathophysiological situations in essential hypertension, supports the view ofaldosterone as a potential cardiovascular toxin and indicates the use of mineralocorticoid receptor blockers in resistant hypertension and patients with cardiovascular or renal organ damage.
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PMID:[Aldosterone as an endogenous cardiovascular toxin and the options for its therapeutic management]. 2227 34

Large artery stiffness, as measured by pulse wave velocity, is correlated with high blood pressure and may be a causative factor in essential hypertension. The extracellular matrix components, specifically the mix of elastin and collagen in the vessel wall, determine the passive mechanical properties of the large arteries. Elastin is organized into elastic fibers in the wall during arterial development in a complex process that requires spatial and temporal coordination of numerous proteins. The elastic fibers last the lifetime of the organism but are subject to proteolytic degradation and chemical alterations that change their mechanical properties. This review discusses how alterations in the amount, assembly, organization, or chemical properties of the elastic fibers affect arterial stiffness and blood pressure. Strategies for encouraging or reversing alterations to the elastic fibers are addressed. Methods for determining the efficacy of these strategies, by measuring elastin amounts and arterial stiffness, are summarized. Therapies that have a direct effect on arterial stiffness through alterations to the elastic fibers in the wall may be an effective treatment for essential hypertension.
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PMID:Elastin in large artery stiffness and hypertension. 2229 Jan 57

Urinary type IV collagen excretion (uT4C) in diabetic patients is higher than in normal subjects. In this study, we investigated the relationship between uT4C and renal hemodynamics in 42 patients with essential hypertension. The renal resistive index (RI) is calculated from blood flow velocities measured using pulsed-wave in interlobar arteries. There was a significant correlation between uT4C to creatinine ratio (uT4C/uCr) and age, hemoglobin A1c (HbA1c), and RI. A stepwise regression analysis showed that RI was independently associated with uT4C/uCr. These results indicated that uT4C may be a marker of renovascular stiffness due to glomerulosclerosis in patients with essential hypertension.
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PMID:Relationship between renal hemodynamics and urinary type IV collagen in patients with essential hypertension. 2256 77

Aldosterone overproduction increases arterial wall stiffness by accumulation of different types of collagen fibres and growth factors. Our previous studies showed that central (aortic) arterial stiffness is increased in primary aldosteronism (PA) independently of concomitant hypertension and that these changes might be reversible after successful adrenalectomy. There is limited data available on the potential impact of mineralocorticoid overproduction on the deterioration of peripheral arterial stiffness. The current study was thus aimed at investigating the effect of aldosterone overproduction on peripheral arterial stiffness assessed by peripheral (femoral-ankle) pulse wave velocity (PWV) in PA patients compared with essential hypertension (EH) patients. Forty-nine patients with confirmed PA and 49 patients with EH were matched for age, blood pressure, body mass index, lipid profile, and fasting glucose. PWV was obtained using the Sphygmocor applanation tonometer. Both peripheral and central PWV were significantly higher in PA patients compared to EH patients, while clinical blood pressures were similar. Plasma aldosterone level was the main predictor of peripheral PWV in PA. Our data indicate aldosterone overproduction in PA does not preferentially affect central arterial system. Fibroproliferative effect of higher aldosterone levels lead to alteration of central-elastic as well as peripheral-muscular arteries with subsequent increase in its stiffness.
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PMID:Peripheral arterial stiffness in primary aldosteronism. 2288 Dec 32


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