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 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A large-scale, 8-week, open-label, clinical experience trial evaluated the efficacy of the angiotensin II receptor (AT1 subtype) blocker candesartan cilexetil (16 to 32 mg once daily) either alone or as add-on therapy in 6465 hypertensive patients. The study population was 52% female and 16% African American with a mean age of 58 years. It included 5,446 patients who had essential hypertension (HBP) and 1,014 patients who had isolated systolic hypertension (ISH). These patients had either untreated or uncontrolled hypertension (systolic blood pressure [SBP] 140 to 179 mm Hg or diastolic blood pressure [DBP] 90 to 109 mm Hg inclusive at baseline) despite a variety of antihypertensive medications including diuretics, calcium antagonists, angiotensin converting enzyme (ACE) inhibitors, and alpha- or beta-blockers, either singly or in combination. The mean baseline blood pressure for the HBP group was 156/97 mm Hg. Candesartan cilexetil as monotherapy (in 51% of HBP patients) reduced mean SBP/DBP by 18.7/ 13.1 mm Hg. As add-on therapy (in 49% of HBP patients) to various background therapies, candesartan cilexetil consistently reduced mean SBP/DBP further, irrespective of the background therapy: diuretics (17.8/11.3 mm Hg), calcium antagonists (16.6/11.2 mm Hg), beta-blockers (16.5/ 10.4 mm Hg), ACE inhibitors (15.3/10.0 mm Hg), alpha-blockers (16.4/10.4 mm Hg). The mean baseline blood pressure for the ISH group was 158/81 mm Hg. Candesartan cilexetil, as monotherapy (in 34% of ISH patients), reduced SBP/DBP by 17.0/4.4 mm Hg. As add-on therapy (in 66% of ISH patients) to various background therapies, candesartan cilexetil consistently reduced mean SBP/DBP further, irrespective of the background therapy: diuretics (17.4/5.1 mm Hg), calcium antagonists (15.6/3.6 mm Hg), beta-blockers (14.0/4.8 mm Hg), ACE inhibitors (13.4/4.3 mm Hg), and alpha-blockers (11.6/4.5 mm Hg). The further blood pressure lowering effects of candesartan cilexetil as add-on therapy were seen regardless of age, sex, and race. Overall, 6.8% of the 6465 patients withdrew because of adverse events, most commonly headache (6.3%) and dizziness (5.0%). Orthostatic hypotension was infrequent; 0.2% with candesartan cilexetil alone, and 0.8% with candesartan cilexetil as add-on therapy. Thus, candesartan cilexetil either alone or as add-on therapy was highly effective for the control of systolic or diastolic hypertension regardless of demographic background when used in typical clinical practice settings.
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PMID:Efficacy of candesartan cilexetil as add-on therapy in hypertensive patients uncontrolled on background therapy: a clinical experience trial. ACTION Study Investigators. 1141 37

The renin-angiotensin system (RAS) is involved in a complex mechanism that serves to preserve the blood supply to organs so that they can maintain cellular function. Angiotensin II exerts this effect, independently of the blood pressure generated, through two time-related events: a fast opening of the reserve collateral circulation and a much slower response of new vessel formation or angiogenesis. This effect is observed in rats with ligation of the abdominal aorta and in gerbils with abrupt or progressive unilateral carotid artery ligation. Inhibition of the angiotensin-converting enzyme (ACE) or the angiotensin II receptor represses this effect, and it appears that it is mediated through a non-AT1 receptor site of angiotensin II. Many tumors, both benign and malignant, express renin and angiotensin. It seems that the stimulating action of angiotensin II on angiogenesis could also be involved in preserving the blood supply to tumor cells. Administration of converting enzyme inhibitors increases survival and decreases tumor size in tumor-bearing rats. These observations support the hypothesis that the RAS, directly or indirectly, is involved in situations in which the restoration of blood supply is critical for the viability of cells and that it is present not only in normal but also in pathological conditions such as tumors. In view of the ubiquitous presence of renins and angiotensins, it is also likely to be involved in other conditions, such as inflammation, arthritis, diabetic retinopathy, and retrolental fibroplasia, among others in which angiogenesis is prominent. In addition, angiotensin II could be involved, through the counterbalance of the AT1 and AT2 receptors, in the rarefaction of blood vessels as an etiologic component of essential hypertension.
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PMID:Protection against ischemia: a physiological function of the renin-angiotensin system. 1143 99

Control of hypertension is hindered by the incidence of adverse events associated with therapy, which can result in low patient compliance. Specific angiotensin II receptor subtype AT1 blockers offer an alternative to the angiotensin converting enzyme inhibitors in the treatment of hypertension, as the incidence of side-effects may be lower. This open-label study was designed to investigate the long-term safety and efficacy of the AT1 receptor blocker, eprosartan, in patients with mild to moderate essential hypertension (sitting diastolic blood pressure > or = 95 mmHg and < or = 114 mmHg). 706 patients from 55 centres in the USA and three centres in Canada were randomised to receive once-daily eprosartan (400-800 mg) alone or in combination with hydrochlorothiazide (HCTZ). The study consisted of five periods: screening (day 1), run-in (2-4 weeks), titration (3-15 weeks), maintenance (12-24 months) and follow-up (5-7 days). Safety evaluations included incidences of adverse events and changes in laboratory tests, vital signs and electrocardiograms. Efficacy assessments included effects on blood pressure (BP) and fasting concentrations of lipids and glucose. The maintenance period was completed at 12 months by 583 (83.3%) patients and at 24 months by 311 (44.4%) patients. In total, 396 (56.1%) patients completed the study according to protocol. Once-daily eprosartan was well tolerated either alone or in combination with HCTZ, irrespective of the study dose administered. Patients treated with eprosartan had a safety profile similar to that reported in short-term placebo-controlled studies. The most frequently reported adverse event was upper respiratory tract infection. The incidence of adverse events was not affected by age or race, and, although events increased with the addition of HCTZ, they were generally not severe. The beneficial effect on BP was maintained throughout treatment. For the majority of patients, HDL cholesterol, triglyceride and glucose levels remained within the reference levels at all doses and timepoints. In summary, eprosartan provides reliable blood pressure control in a high proportion of patients, with a safety profile similar to that seen with placebo in short-term, placebo-controlled trials. By providing long-term safety and efficacy, eprosartan may have the potential to increase patient compliance, a significant issue in the treatment of hypertension in all patient types.
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PMID:Eprosartan provides safe and effective long-term maintenance of blood pressure control in patients with mild to moderate essential hypertension. 1146 50

Recent evidence shows that leptin may contribute to elevated blood pressure (BP) and interact with the renin-angiotensin-aldosterone and cellular immune systems. Altered T-cell activities and changes in T-cell subset ratios have also been reported in hypertension. However, little is known about the effects of AT1-receptor antagonism on T-cell activities and plasma leptin concentrations in primary hypertension. We have, therefore, investigated the relationship between leptin and T-cell activities and the effect of an AT1-receptor antagonist, losartan, in primary hypertension. Twenty recently-diagnosed and untreated young adults (11 males and 9 females, age; 39.9+/-7.6 years, range 23-49 years, BMI; 27.6+/-3.7kg/m2) and 20 normotensive healthy, age-, sex- and BMI-matched controls were studied. The [3H]-thymidine uptakes of cultured lymphocytes were determined, both spontaneously and after stimulation with phytohaemagglutinin. The tests were performed before and after three months of treatment with losartan. The results indicate that the blastogenic responses of T-cells to phytohaemagglutinin are significantly higher in the patient group compared with controls (p=0.02). After normalisation of BP, T-cell responses were significantly reduced and were lower than in the controls (p=0.01). Pretreatment plasma leptin levels were significantly higher in hypertensives than in controls (p=0.01). However, losartan treatment had no significant effect on leptin concentrations; moreover, no correlation between leptin levels and T-cell activity was found. Our data show that plasma leptin levels and T-cell activity are markedly enhanced in untreated essential hypertension and that the alteration of T-cell activity is not related to plasma leptin levels. Antihypertensive treatment with losartan decreases T-cell activities but does not influence plasma leptin levels. We conclude that leptin levels are not affected by AT1-receptor blockade and are not related to T-cell activity.
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PMID:Effects of losartan treatment on T-cell activities and plasma leptin concentrations in primary hypertension. 1188 Nov 9

The aim of this study was to evaluate the medium-term effects of the selective AT1-blocker irbesartan on atrial natriuretic peptide (ANP) levels in patients with moderate essential hypertension. The drug was given orally in a daily dose of 300 mg for 30 days. Plasma ANP levels increased by 15.7% despite the drop in blood pressure and the slight decrease of atrial and ventricular diameters. These findings indicate that AT,-blockers like irbesartan exert part of their antihypertensive action by increasing ANP plasma levels.
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PMID:Plasma atrial natriuretic peptide in essential hypertension after treatment with irbesartan. 1203 77

Essential hypertension, a major health problem worldwide, is a disease generally considered to require life-long treatment. However, evidence suggests that hypertension is caused by specific phenotypic changes caused by the combination of genetic and environmental factors. Thus, in principle, hypertension could be prevented by prevention of these phenotypic changes. Animal data indicate that early treatment that blocks the renin-angiotensin system have long-term effects after treatment withdrawal. Here we report on two human trials that are testing whether early treatment (with the AT1-antagonist, candesartan) is able to have a persistent effect after stopping treatment: the Danish Hypertension Prevention Project and Trial of Prevention of Hypertension.
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PMID:Can hypertension be prevented? The Danish Hypertension Prevention Project and the Trial of Prevention of Hypertension studies. 1215 73

Measurement of regional sympathetic activity with nerve recording and noradrenaline spillover isotope dilution techniques demonstrates activation of the sympathetic nerves of the heart, kidneys and skeletal muscle vasculature in younger patients with essential hypertension. Sympathetic overactivity in the renal sympathetic outflow is a prominent pathophysiological feature in obesity-related hypertensives of any age. This increase in sympathetic activity is thought to both initiate and sustain the blood pressure elevation, and, in addition, contributes to adverse cardiovascular events. Sympathetic overactivity seems to particularly influence systolic pressure, by increasing the rate of left ventricular ejection, by reducing arterial compliance through increasing neural arterial tone, and via arteriolar vasoconstriction, by promoting rebound of the reflected arterial wave from the periphery. Inhibition of the renin-angiotensin system in certain circumstances appears to be able to reduce sympathetic nervous activity. Claims have been made for such an action at virtually every site in the sympathetic neuraxis. In reality, renin-angiotensin actions on the sympathetic nervous system are probably much more circumscribed than this, with the case perhaps being strongest for a presynaptic action of angiotensin on sympathetic nerves, to augment noradrenaline release. The ability of angiotensin receptor blockers to antagonize neural presynaptic angiotensin AT1 receptors appears to differ markedly between the individual agents in this drug class. In experimental models, such as the pithed rat, neural presynaptic actions are particularly evident with eprosartan. In a blinded study of crossover design, the effects of eprosartan and losartan on sympathetic nerve firing, measured by microneurography, and whole body noradrenaline spillover to plasma is currently being measured in patients with essential hypertension. A reduction in noradrenaline spillover disproportionate to any possible fall in nerve firing would document the presence of presynaptic antagonism of noradrenaline release.
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PMID:Differentiation in the effects of the angiotensin II receptor blocker class on autonomic function. 1218 59

The aim of this study was to investigate blood pressure, renal haemodynamics, hormone secretion and the responses to angiotensin II infusion during candesartan cilexetil (candesartan), losartan potassium (losartan) and valsartan treatment in patients with essential hypertension. In this double-blind, randomized, crossover study, 24 patients (mean blood pressure of 163/97 mmHg), received candesartan 16 mg, losartan 50 mg and valsartan 80 mg once daily (o.d.) for 4 weeks after a placebo run-in period. At the end of each period, angiotensin II (0.5, 1.0 and 1.5 ng/min/kg) was infused 24 h after the previous drug administration. Each dose of angiotensin II was infused for 45 min. Before infusion and at the end of each infusion step, blood pressure and renal haemodynamics were assessed and plasma renin activity and plasma concentrations of angiotensin II and aldosterone were measured. During treatment with candesartan, resting mean arterial pressure (mean +/- SEM, 106 +/- 2 mmHg) was significantly decreased compared with treatment with losartan (110 +/- 2 mmHg) and valsartan (109 +/- 2 mmHg). Candesartan inhibited the angiotensin II induced increase in filtration fraction (0.8 +/- 0.4%) significantly more than losartan (1.5 +/- 0.4%) and valsartan (1.6 +/- 0.4%) and reduced the increase in aldosterone secretion (17 +/- 5 pg/ml/) significantly more than losartan (74 +/- 17 pg/ml/) and valsartan (82 +/- 19 pg/ml/). In conclusion, candesartan 16 mg o.d. reduced resting blood pressure significantly more than losartan 50 mg o.d. and valsartan 80 mg o.d. Candesartan almost completely inhibited the exogenous angiotensin II induced renal vasoconstriction, effectively inhibited the increase in filtration fraction and significantly blunted aldosterone secretion compared with losartan and valsartan, indicating a more effective AT1 receptor blockade with candesartan.
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PMID:Influence of AT1 receptor blockade on blood pressure, renal haemodynamics and hormonal responses to intravenous angiotensin II infusion in hypertensive patients. 1236 Nov 94

OBJECTIVE: To investigate the relation of renin-angiotensin system (RA3) gene polymorphisms and expressions with the clinical efficacy of antihypertensive drugs. METHODS: This randomized, single-blind study consisted of 90 patients with essential hypertension, who were divided into losartan, lisinopril and nisodipine groups with corresponding medications as indicated. The genotypes of angiotensin-converting enzyme (ACE) insertion/deletion, angiotensinogen (AGT) M235T polymorphism and expressions of ACE and AT1 receptor genes were examined individually. RESULTS: The basal level of mRNA expression of AT1 receptor was lower in patients with MM genotype of AGT gene than those in patients with MT 1 and TT genotypes, but between the latter two, no significant differences were found. The three antihypertensive drugs, when significantly lowering the blood pressure, reduced AT1 receptor mRNA expression concurrently. Losartan and lisinopril both decreased ACE mRNA expression levels that were positively correlated with the difference of the diastolic blood pressure whereas nisodipine elevated ACE mRNA expression, showing inverse correlation to the difference of thediastolic blood pressure. CONCLUSION: For patients with hypertension who have elevated basal levels of AT1 mRNA expression and AGT T allele or who retain high basal expression levels of ACE mRNA AT1 antagonists and ACE inhibitors that execute their action through RAS are preferentially selected, and in cases of low basal levels of ACE mRNA calcium antagonists are preferred.
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PMID:Relation of renin-angiotensin system gene polymorphisms and expressions with the efficacy of antihypertensive drugs. 1242 59

Valsartan (Diovan) is a potent, orally active, specific, and highly selective blocker for the AT1-receptor subtype. The antihypertensive effects of oral treatment with valsartan were preclinically demonstrated in the sodium-depleted marmosets, renal hypertensive rats (2K1C), spontaneous hypertensive rats (SHR) and stroke-prone SHR. Moreover, valsartan had protective effects against hypertensive end-organ damage such as cardiac hypertrophy and renal disease. In an investigation of pharmacokinetics and pharmacodynamics in normotensive male volunteers, valsartan was rapidly absorbed with the maximal plasma concentration occurring 2-3 h after oral administration. The elimination half-life was about 4-6 h, valsartan was poorly metabolized, and most of the drug was excreted via feces. Valsartan produced persistent reductions of blood pressure in patients with mild to moderate essential hypertension and had a good safety profile with a wide therapeutic window between the effective pharmacological doses and the toxic doses. Therefore, valsartan is expected to be a safe and effective antihypertensive agent for the treatment of essential and severe hypertension.
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PMID:[Preclinical and clinical profile of Valsartan, a selective angiotensin II type-1 receptor blocker]. 1249 11


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