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

Arterial wall stiffness, an important independent risk factor for cardiovascular disease in patients with hypertension, is worsened by the coexistence of diabetes mellitus. This randomised, prospective, double-blind, crossover trial assessed the effects of telmisartan on arterial stiffness in patients with Type 2 diabetes with essential hypertension. After a two-week placebo wash out period, 28 ambulatory patients received telmisartan (40 mg) or placebo for three weeks. Following a second two-week placebo wash out period, patients received the alternate treatment for a further three weeks. Augmentation index and central blood pressure (BP) were determined using the SphygmoCor device and pulse wave velocity (PWV) was measured using an automatic device, the Complior trade mark, at the beginning and the end of each period. Telmisartan significantly reduced the carotid femoral PWV compared with placebo (mean adjusted treatment difference 0.95 m/s; 95% CI: 1.67, 0.23 m/s; p=0.013). Peripheral and central diastolic, systolic and pulse pressures were also significantly reduced with telmisartan compared with placebo. In conclusion, telmisartan reduces arterial stiffness and peripheral and central BPs as assessed by PWV and pulse contour analysis in hypertensive patients with Type 2 diabetes. These properties of telmisartan suggest that it may improve cardiovascular outcome in this patient population.
J Renin Angiotensin Aldosterone Syst 2002 Sep
PMID:Effects of telmisartan on arterial stiffness in Type 2 diabetes patients with essential hypertension. 1256 68

Renin-angiotensin system reactivity and the constitutive capacity of the renal tubule to reabsorb sodium play a role in the individual response to diuretic therapy; therefore we evaluated the blood pressure (BP) response to hydrochlorothiazide in 87 never-treated individuals with mild essential hypertension, according to ACE gene I/D and alpha-adducin Gly460Trp polymorphism. These genotypes where chosen because previous data showed their interaction in determining the BP response to salt probably was the result of their involvement in the activation of the renin-angiotensin system (ACE) and in the constitutive capacity of the kidney to reabsorb sodium (alpha-adducin) (treatment for 2 months). BP was measured after 3 run-in visits and after the first and second months of treatment by means of a standardized procedure. Data were analyzed by ANOVA, t test, and multivariate ANOVA for repeated measures (covarying for gender, age, and body mass index). Although basal mean BP (MBP) was similar in the different ACE and alpha-adducin genotypes, patients carrying at least one I allele of ACE and one 460Trp allele of alpha-adducin had the largest MBP decrease with treatment (12.7+/-1.9 mm Hg), the effect of the combination of genotypes being additive but not epistatic. These patients had an odds ratio of 15.75 of being a responder to hydrochlorothiazide compared with patients with Gly460Gly+DD, with the least MBP decrease (3.4+/-1.7 mm Hg). Alpha-adducin and ACE I/D polymorphism may be useful to predict the interindividual degree of response to hydrochlorothiazide; the analysis of the combination of the 2 genotypes increases the accuracy of the prediction of response to the drug.
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PMID:ACE and alpha-adducin polymorphism as markers of individual response to diuretic therapy. 1262 34

Mineralocorticoid receptor (MR) blockade is effective in reducing total mortality and the incidence of heart failure in patients with systolic left ventricular dysfunction (SLVD) associated with chronic heart failure or post myocardial infarction. Pre-clinical and clinical studies in SLVD have shown that MR blockade reduces sudden cardiac death, left ventricular remodelling, left ventricular hypertrophy, endothelial dysfunction, autonomic imbalance, renal dysfunction and improves fibrinolysis. While MR blockade promotes sodium excretion and the combination of an angiotensin-converting enzyme inhibitor and a MR blocker have been shown to be more effective than either alone in causing natriuresis, it is unlikely that their beneficial effects can be explained solely on this basis. Aldosterone has been shown to have a number of adverse effects, including activation of other neurohumeral mediators, stimulation of active reactive oxygen species (ROS), activation of the NF-Greek small letter kappa kappabeta and AP-1 signalling pathways, vascular inflammation and fibrosis, myocardial hypertrophy, autonomic imbalance, and a decrease in fibrinolysis. MR blockade is, however, effective both in situations with and without an increase in serum aldosterone level, since the MR can be occupied and activated by cortisol as well as by aldosterone. In view of these mechanisms, MR blockade may play an important role not only on SLVD, but also in essential hypertension with normal systolic function, diastolic heart failure, valvular heart disease, vascular stiffening with ageing, progression of renal disease, and diabetes mellitus. This hypothesis will, however, require further prospective evaluation.
J Renin Angiotensin Aldosterone Syst 2003 Sep
PMID:Mineralocorticoid receptor blockade: new insights into the mechanism of action in patients with cardiovascular disease. 1460 20

The Telmisartan Effectiveness on Left ventricular MAss Reduction (TELMAR) trial will assess the effect of the angiotensin II (Ang II) receptor blocker, telmisartan, on left ventricular hypertrophy (LVH) compared with the b-blocker, metoprolol, at similar antihypertensive doses. The rationale is that antihypertensives reduce LVH, a cardiac adaptation to pressure overload, principally by pressure-related effects. Ang II plays a key role in pressure-independent mechanisms causing LVH, and angiotensin-converting enzyme (ACE) inhibitors induce more pronounced LVH regression than some other antihypertensives. Blocking Ang II Type 1 receptors may be more effective than ACE inhibition in reducing LVH. TELMAR is a prospective, randomised, double-blind, double-dummy, parallel-group trial. A total of 140 patients (age 18 80 years) with uncontrolled essential hypertension (mean daytime systolic blood pressure [SBP] >140 mmHg or diastolic blood pressure [DBP] >90 mmHg and/or night-time SBP >120 mmHg or DBP >70 mmHg, measured by ambulatory blood pressure monitoring [ABPM]) and left ventricular mass index related to height (LVMI) >0.8 g/cm for females, >1.1 g/cm for males (defined by magnetic resonance imaging [MRI]) will be randomised to once-daily telmisartan or metoprolol. The telmisartan dose will be 40 mg for the first two weeks, 80 mg for 5.5 months and 40 mg for the last two weeks. Metoprolol will be given at a dose of 47.5 mg for two weeks, 95 mg for 5.5 months and 47.5 mg for two weeks. Concomitant add-on medication with hydrochlorothiazide and amlodipine will be allowed. The primary endpoint is the percentage change in LVMI at treatment end versus baseline, using MRI. Secondary variables include blood pressure changes and response rates assessed by ABPM and manual cuff sphygmomanometry, and end-systolic wall stress, systolic left ventricular function (LVF) and diastolic LVF determined by MRI. A separate study was performed prior to the main trial to define the normal range of MRI data in an age-matched population.
J Renin Angiotensin Aldosterone Syst 2003 Dec
PMID:Reduction (TELMAR) as assessed by magnetic resonance imaging in patients with mild-to-moderate hypertension--a prospective, randomised, double-blind comparison of telmisartan with metoprolol over a period of six months rationale and study design. 1468 71

Essential hypertension is a multifactorial disease in which genetic and enviromental factors play an important role. These factors differ in each population. As there are no existing data for the Turkish population, we investigated four Renin Angiotensin System (RAS) gene polymorphisms, the angiotensin converting enzyme (ACE), angiotensinogen (AGN) M235T/T174M and angiotensin II type 1 receptor A1166C polymorphism in 109 hypertensive and 86 normotensive Turkish subjects. Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP), and agarose gel electrophoresis tecniques were used to determine these polymorphism. The frequencies of person that carry ACE D allel (DD+ID) was significantly higher in hypertensive group (99.1%) than controls (80%) (P 0.000). M235T TT genotype was also found significantly higher in hypertensives than control group (20% vs 2.7%; P 0.001). The frequency of AGN 174M allele was higher in the hypertensive group than control subjects (8.76% vs 4.81%). Frequency of ATR1 C allele (AC+CC genotypes) was found higher hypertensives than controls (39.4% vs 25.9%; P = 0.054). Our results suggest that an interaction exists between the RAS genes and hypertension in Turkish population.
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PMID:Angiotensin converting enzyme I/D, angiotensinogen T174M-M235T and angiotensin II type 1 receptor A1166C gene polymorphisms in Turkish hypertensive patients. 1474 33

Arterial stiffness has recently been recognised as an independent risk factor for cardiovascular morbidity and mortality in hypertension. Many of the complications seen with angiotensin II (Ang II) excess or hyperaldosteronism--an increased event rate, left ventricular hypertrophy, endothelial dysfunction and target organ damage--are also associated with arterial stiffness. It is possible that reduced arterial compliance may be one mechanism whereby increased activity of the renin-angiotensin-aldosterone system (RAAS) produces adverse vascular effects. Common pathophysiological processes, altered collagen turnover and increased fibrosis may underlie both arterial stiffness and RAAS-associated vascular damage. While it is recognised that patients with hyperaldosteronism have increased arterial stiffness, the role of the RAAS in modulating arterial compliance in essential hypertension and in normotensive subjects is less clear cut. There is, however, more consistent data which show that drugs that interfere with Ang II or aldosterone, namely angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and aldosterone antagonists, all reduce arterial stiffness. In many cases, this is to a greater extent than predicted from the extent of reduction in blood pressure (BP), suggesting a role for RAAS in vascular stiffness in hypertensive subjects. There is also evidence that combined ACE inhibitors (ACE-Is) and ARBs may have an additive effect in reducing stiffness. The reduction in cardiovascular mortality in end-stage renal disease patients treated with ACE-Is was preferentially seen in those who had reduced arterial stiffness. These data suggest that, in addition to regulation of vascular biology and BP, the RAAS is an important determinant of arterial stiffness in health and, more particularly, in disease.
J Renin Angiotensin Aldosterone Syst 2004 Sep
PMID:Arterial stiffness and the renin-angiotensin-aldosterone system. 1552 44

The development of essential hypertension (EH) is proposed to be the result of a cascade of metabolic alterations, with high insulin levels/hyperinsulinemia and an abnormal reaction to the vasodilatory effect of insulin as the initiating factors. It is well established that insulin causes vasodilatation of peripheral resistance vessels. In normal subjects, this insulin-induced vasodilatation and decrease of the peripheral vascular resistance (PVR) is compensated by an SNS-mediated re-vasoconstriction in order to avoid hypotension, with the net effect of a slight decrease in blood pressure and no significant effect on peripheral vascular resistance. In contrast, in genetically predisposed subjects, prone to the development of essential hypertension, the insulin-induced vasodilatation is compensated by an increased heart rate and cardiac output (to avoid hypotension), mediated by an abnormal sympathetic overactivity, (characterised by high norepinephrine spillover rates and (frequently) a hyperdynamic circulation), while the PVR remains low during the early phase of developing EH. During the course of chronic hypertension, the SNS-overactivity leads to progressive trophic alterations of vessel walls, and structural and functional vascular remodeling, with narrowing of arterial resistance vessels and an increasing PVR. Vascular remodeling and lumen narrowing not only affect peripheral resistance vessels, but also kidney vessels. Narrowing and decreased distensibility of preglomerular kidney vessels lead to chronic activation of the Renin-Angiotensin-Aldosterone-System, with reinforcement and fixation of hypertension. High-glycemic index nutrition is suggested to play a key role in the etiology of hypertension: The chronic stimulus of pancreatic beta-cells due to high-glycemic index nutrition may cause cell hypertrophy and dysfunction, resulting in postprandial hyperinsulinemia, and -- in susceptible subjects -- the development of EH. Since significant evidence suggests that hyperinsulinemia also represents a key factor for the development of obesity, insulin resistance and the metabolic syndrome, the well-known common association of EH and these metabolic alterations becomes quite understandable.
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PMID:Pathogenesis and etiology of essential hypertension: role of dietary carbohydrate. 1569 97

Raised blood pressure (BP) is extremely common in individuals with autosomal dominant polycystic kidney disease (ADPKD) and is almost invariably raised once they develop renal failure. The underlying mechanisms for the rise in BP in individuals with ADPKD are unclear. The progressive number and enlargement of renal cysts, causing structural damage to the kidneys and, thereby, affecting tubular function as well as causing distortion of the glomeruli and renal ischaemia, is likely to be of primary importance. There is some evidence from animal models that there may be over-activity of the intra-renal renin-angiotensin system (RAS) that could account for the rise in BP. Studies in man have shown conflicting results, but a recent more carefully controlled study using both measurements of activity and pharmacological blockade of the RAS clearly demonstrated no evidence of over-activity of the circulating RAS in ADPKD compared to matched individuals with essential hypertension. A more likely explanation for the rise in BP that occurs in ADPKD is retention of sodium and water due to tubular damage. Disappointingly, in spite of good evidence that RAS blocking drugs slow the progression of other renal, particularly glomerular, diseases, there is little evidence to suggest this is true for patients with ADPKD. Nevertheless, there is no doubt that lowering BP in ADPKD is just as important, if not more important, as in essential hypertension to prevent cardiovascular disease and strokes, with a recommended BP target of < 120/80 mmHg.
J Renin Angiotensin Aldosterone Syst 2006 Sep
PMID:Autosomal dominant polycystic kidney disease: role of the renin-angiotensin system in raised blood pressure in progression of renal and cardiovascular disease. 1709 50

The antihypertensive efficacy and tolerability of combination therapy with candesartan cilexetil, 16 mg plus hydrochlorothiazide (CC/HCTZ), 12.5 mg was compared with that of amlodipine, in a multicentre, double-blind, randomised, parallel-group study in patients with mild-to-moderate essential hypertension inadequately controlled by monotherapy. After a two week run-in period on existing therapy, patients with a sitting diastolic blood pressure (DBP) of 90-110 mmHg and a sitting systolic blood pressure (SBP) <or= 180 mmHg were switched to either CC/HCTZ (n=101) or amlodipine (n=102), once-daily by mouth. After eight weeks of treatment, both regimens reduced mean trough blood pressure (BP) by a similar amount: mean sitting SBP/DBP reductions were -15.4/-11.9 mmHg for CC/HCTZ, and -15.7/-12.0 mmHg for amlodipine (group differences, p=0.835/0.963). The BP of 84.2% of patients on CC/HCTZ and 84.5% on amlodipine was controlled (sitting DBP < 90 mmHg and sitting SBP < 140 mmHg) (p=1.00). Six (5.9%) patients on CC/HCTZ and 18 (17.6%) on amlodipine discontinued treatment, including one (1%) and 13 (12.7%) owing to adverse events (p<0.001). The most common adverse event was peripheral oedema, which occurred in two patients on CC/HCTZ and 19 on amlodipine. In conclusion, CC/HCTZ and amlodipine were equally effective in reducing BP in hypertensive patients not controlled by monotherapy, but CC/HCTZ was much better tolerated. Tolerance is an important clinical consideration in the chronic treatment of an asymptomatic disease.
J Renin Angiotensin Aldosterone Syst 2007 Sep
PMID:Efficacy and tolerability of candesartan cilexetil/hydrochlorothiazide and amlodipine in patients with poorly controlled mild-to-moderate essential hypertension. 1790 2

Renin-angiotensin (RAS) genes, a group of promising candidate genes involved in essential hypertension (EH), play a key role in blood pressure regulation. Recently, a series of novel RAS gene polymorphisms were reported, which significantly influence the rate of the gene transcription. This study was designed to explore the association between the RAS gene polymorphisms and EH in a remote countryside population. We examined six polymorphisms in the main component genes of RAS: angiotensin-converting enzyme (ACE) (I/D), angiotensinogen (AGT) (A-6G, A-20C, G-217A and T174 M) and angiotensin type 1 receptor (AT1R) (A1166C). Six polymorphisms were genotyped by gene chip technology. Association studies were performed in 220 EH patients and 235 normotensives. Our results revealed that AGT A-6G, T174 M and ACE-I/D were significantly associated with EH (AGT A-6G: AG+GG vs AA; OR=1.36; 95% CI=1.04-1.77. T174M: CT+TT vs CC; OR=1.45; 95% CI=1.15-1.90. ACE I/D: ID+DD vs II; OR=1.171; 95% CI=1.00-1.37). Moreover the logistic regression analysis suggested that the haplotype of AGT -6A, 174C, -217G and -20A might decrease the risk of EH (OR=0.64; 95% CI=0.49-0.83), after adjusting the confounding factors of gender, age and BMI. In conclusion, the AGT A-6G, T174 M and ACE I/D polymorphisms are associated with EH and the AGT haplotype -6A, 174C, -217G and -20A decrease the risk of EH in the southern Chinese population.
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PMID:Association between renin-angiotensin system gene polymorphism and essential hypertension: a community-based study. 1883 Feb 50


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