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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin II can induce oxidant stress by stimulating vascular superoxide production. Hypertension promotes mitochondrial function decline in brain, liver and heart. The aim of this study was to investigate whether a) hypertension is associated to kidney mitochondrial dysfunction, and b) angiotensin II blockade can reverse potential mitochondrial changes in hypertension. Four-month-old male spontaneously hypertensive rats (SHR) received drinking water containing candesartan (7.5 mg/kg/day, SHR+Cand), or no additions (SHR) for 4-months. Eight-month-old Wistar-Kyoto rats (WKY), that received water with no additions, were used as control. Systolic blood pressure, proteinuria, cortical glomerular area, and glomerular and tubulointerstitial alpha-smooth muscle actin labeling, were significantly higher, and creatinine clearance was significantly lower, in SHR relative to WKY and SHR+Cand. In SHR, kidney mitochondria membrane potential, and nitric oxide synthase and cytochrome oxidase activities were significantly lower than in WKY and SHR+Cand. In SHR, mitochondrial hydrogen peroxide production was significantly higher than in WKY and SHR+Cand. The results suggest that, in hypertension, increased mitochondrial oxidant production may mediate kidney mitochondria dysfunction. Candesartan preserved mitochondrial function, probably favoring the maintenance of adequate cellular and tissue function in the kidney. The known renal protective effects of candesartan in hypertension may be related to the improvement of mitochondrial function. This may be an additional or alternative explanation for some of the beneficial effects of AT1 receptor antagonists.
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PMID:Angiotensin II blockade improves mitochondrial function in spontaneously hypertensive rats. 1630 82

Diabetic retinopathy is characterized by both functional and morphological changes in the retinal microvessels that can lead to macular edema, neovascularization, and vision loss. Hypertension has been identified as a major risk factor for diabetic retinopathy and randomized clinical trials have shown that reduction of blood pressure using angiotensin converting enzyme (ACE) inhibitors reduces the progression of diabetic retinopathy. The major components of the renin-angiotensin system have been identified in ocular tissues. Activation of angiotensin II type 1 (AT1) receptors expressed on retinal endothelial cells and pericytes has been implicated in contributing to the microvascular abnormalities in diabetic retinopathy. We have examined the experimental and clinical evidence for the role of the renin-angiotensin system in the pathogenesis of diabetic retinopathy, including the effects of ACE inhibition and AT1-receptor antagonism on diabetes-induced abnormalities in retinal hemodynamics, vascular permeability, and leukostasis; retinal neovascularization in rodent models of oxygen-induced retinopathy; and results from randomized clinical trials that have investigated the effects of ACE inhibitors on the progression of diabetic retinopathy in diabetic patients in the absence or presence of hypertension. The effects of AT1-receptor antagonism on the retina have been attributed to decreases in systemic blood pressure and the concomitant reduction in mechanical vascular stretch, in addition to the intraocular effects blocking AT1-receptor stimulation of retinal endothelial cells and pericytes. Results from the current DIabetic REtinopathy Candesartan Trials program will evaluate the potential of the AT1-receptor as a therapeutic target for diabetic retinopathy.
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PMID:Role of the angiotensin II type 1 receptor in the pathogenesis of diabetic retinopathy: effects of blood pressure control and beyond. 1660 77

The Study on Cognition and Prognosis in the Elderly (SCOPE) assessed the effect of candesartan on cardiovascular and cognitive outcomes in elderly patients (aged 70-89 years) with mild to moderate hypertension. Patients were randomized to treatment with candesartan 8-16 mg daily (n = 2477) or placebo (n = 2460) and followed for 3.7 years on average. In agreement with the study protocol, other antihypertensive drugs were added if blood pressure remained 160 mHg systolic and/or 90 mmHg diastolic. Due to extensive add-on therapy, particularly in patients randomized to placebo, the between-treatment difference in blood pressure was only 3.2/1.6 mmHg. Nevertheless, the main analysis showed that non-fatal stroke was reduced by 28% (p = 0.04) in the candesartan group compared with the control group, and there was a non-significant 11% reduction in the primary endpoint, major cardiovascular events (p = 0.19). This review article presents different predefined and post hoc analyses made so far. Of particular interest are significant risk reductions with candesartan in major cardiovascular events (32%, p = 0.013), cardiovascular mortality (29%, p = 0.049) and total mortality (27%, p = 0.018) in patients who did not receive add-on therapy after randomization, and in whom the difference in blood pressure was 4.7/2.6 mmHg. Other analyses suggest positive effects of candesartan-based treatment on cognitive function, quality of life and new-onset diabetes. In conclusion, SCOPE strongly suggests that candesartan treatment reduces cardiovascular morbidity and mortality in old and very old patients with mild to moderate hypertension. Candesartan-based antihypertensive treatment may also have positive effects on cognitive function and quality of life.
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PMID:Findings and implications of the Study on COgnition and Prognosis in the Elderly (SCOPE) - a review. 1675 69

The prevalence of atrial fibrillation (AF) increases in patients with hypertension. Angiotensin II is involved in structural atrial remodeling, which contributes to the onset and maintenance of AF in paced animal models. We investigated the role of angiotensin II in atrial structural remodeling in rats with hypertension. Ten-week-old male Wistar-Kyoto rats were randomly divided into 4 groups: a control group (no treatment), an Nomega-nitro-L-arginine methyl ester (L-NAME) group (administered L-NAME, an inhibitor of nitric oxide synthase, 1 g/l in drinking water), an L-NAME+candesartan group (L-NAME plus candesartan-an angiotensin II receptor blocker (ARB)-at 0.1 mg/kg/day), and an L-NAME + hydralazine group (L-NAME plus hydralazine at 120 mg/l in drinking water). Eight weeks after treatment, the L-NAME group showed significantly higher systolic blood pressure than the control group (197 +/- 12 vs.138 +/- 5 mmHg, p < 0.05). Candesartan or hydralazine with L-NAME reduced systolic blood pressure to baseline. Chronic inhibition of NO synthesis increased the extent of fibrosis and transforming growth factor-beta expression in atrial tissue, and both of these effects were prevented by candesartan, but not by hydralazine. Cardiac hypertrophy and dysfunction were induced in the L-NAME group, and these effects were also prevented by candesartan, but not by hydralazine. In contrast, the decrease in thrombomodulin expression in the atrial endocardium in hypertensive rats was restored by candesartan and hydralazine. The ARB prevented atrial structural remodeling, a possible contributing factor for the development of AF, in the hearts of rats with hypertension induced by long-term inhibition of NO synthesis.
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PMID:Angiotensin II type 1 receptor blocker prevents atrial structural remodeling in rats with hypertension induced by chronic nitric oxide inhibition. 1677 35

The angiotensin II receptor blockers irbesartan and losartan effectively reduce blood pressure and proteinuria in childhood. We were impressed by the neutral taste and the small size of the candesartan cilexetil tablets. This angiotensin II receptor blocker was used during 4 months in 17 pediatric patients (aged 0.5-16, median 4.5 years) with chronic arterial hypertension (n=6), overt proteinuria (n=2), or both (n=9). The initial candesartan dose of 0.23 (0.16-0.28) mg/kg body weight once daily (median and interquartile ranged) was doubled in ten patients [final dose 0.35 (0.22-0.47) mg/kg body weight]. No adverse clinical experiences were noted on candesartan. Candesartan increased plasma potassium by 0.3 (0.0-0.8) mmol/l (P<0.01). In children with arterial hypertension, blood pressure decreased by 9 (3-13)/9 (3-18) mmHg (P<0.01); in those with overt proteinuria the urinary albumin/creatinine ratio decreased by 279 (33-652) mg/mmol (P<0.05). In conclusion, in children candesartan reduces blood pressure and proteinuria with an excellent short-term tolerability profile.
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PMID:Candesartan cilexetil in children with hypertension or proteinuria: preliminary data. 1680 78

Alterations in the vascular angiotensin II system may play a role in the pathophysiology of vascular disease after menopause. In previous studies we have shown that an increase in tumor necrosis factor (TNF)-alpha levels in aging rats because of estrogen deficiency may result in vascular dysfunction. In this study we investigated the effect of TNF-alpha inhibition in angiotensin II modulation of vascular function in aging female animals. Female rats approaching reproductive senescence (12 to 15 months old) were ovariectomized and treated with placebo, estrogen, or a selective TNF-alpha inhibitor (etanercept) for 4 weeks. Expression of angiotensin II in mesenteric arteries was evaluated by immunofluorescence, and the expression of angiotensin-converting enzyme and angiotensin type I receptor (AT(1)R) was investigated by Western immunoblot. Vascular function was assessed in mesenteric arteries using the myograph system, and the role of endogenous angiotensin II on adrenergic vasoconstriction was evaluated in vitro by selective AT(1)R blockade (Candesartan; 10 micromol/L). Our data demonstrate that estrogen-depleted rats have higher serum levels of TNF-alpha and greater sensitivity to phenylephrine vasoconstriction compared with estrogen-replaced animals, which was attenuated by AT(1)R blockade. In vivo TNF-alpha inhibition or estrogen replacement reduced phenylephrine constriction of mesenteric arteries and decreased the modulation of this vasoconstriction by candesartan. These functional changes were accompanied by a reduction in the vascular expression of angiotensin II, angiotensin-converting enzyme, and AT(1)R. These observations indicate that upregulation of TNF-alpha during estrogen deficiency may contribute to enhance vascular constriction by altering the vascular angiotensin II system.
Hypertension 2006 Sep
PMID:Tumor necrosis factor-alpha and vascular angiotensin II in estrogen-deficient rats. 1686 43

In an effort to assess the cardiovascular benefits of combined angiotensin receptor blockage and calcium channel antagonism, we assessed the chronic effects of the angiotensin type 1 receptor blocker candesartan, the calcium channel blocker benidipine, and the use of a combination therapy in Dahl salt-sensitive (DS) rats. DS rats receiving a high salt diet were treated with either benidipine (4 mg/kg), candesartan (1 mg/kg) or both. Rat blood pressure was measured using a tail-cuff method. Following 12 weeks, the effect on heart weight, plasma-oxidized low-density lipoprotein (ox-LDL) level, endothelium-dependent vasorelaxation, and histology of the heart and aorta was assessed. Blood pressure, heart weight and plasma ox-LDL levels increased, while endothelium-dependent vasorelaxation decreased in the DS rats. Candesartan and benidipine inhibited the increase in blood pressure and heart weight, and the decrease in endothelium-dependent vasorelaxation. The use of benidipine alone or a combination significantly inhibited the increase in ox-LDL levels, whereas candesartan alone had no significant effect on ox-LDL levels. The present findings indicate that, if the monotherapy using ARB could not achieve adequate control of blood pressure, the combination therapy with ARB and benidipine provides the additional reductions in hypertension and cardiac hypertrophy. Moreover, the combination therapy inhibits cardiovascular dysfunction and ox-LDL levels more effectively than use of ARB alone. These results contribute to the possibility of lowering ox-LDL levels as a means of enhancing cardiovascular protection.
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PMID:Effects of combination of angiotensin receptor blocker and calcium channel blocker on ox-LDL levels and cardiovascular dysfunction in Dahl rats. 1686 86

The authors present obtained data on the frequency of genotypes and A and C alleles of polymorphous gene related to Angiotension II first type receptor in patients of Poltava region. These patients were with chronic pyelonephritis and arterial hypertension. Therapeutic efficacy of candesartan treatment of the patients and at the same time their genotypes were considered. Obtained data evidence that AC genotype is more often found among patients with reniparenchymal hypertension, genotype CC is less found among these patients and genotype AA occupies an intermediate place (in 1,7 times less found than among healthy individuals and in 2,2 times more often than among patients with essential hypertension). Candesartan used in monotherapy has a high clinical efficiency in the treatment of patients with AC genotype. Patients with genotype AA and severe course of their disease have to be in a complex treatment or prescribed is applied candesartan in high dosage.
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PMID:[Clinical efficiency of candesartan in patients with renoparenchymal hypertension in dependence on genotype of angeotensin II receptors of I type]. 1731 90

We have evaluated the role of connective tissue growth factor (CTGF) in vascular and renal damage associated with hypertension and possible interactions with angiotensin II (Ang II). Spontaneously hypertensive rats (SHR) were treated with either the Ang II receptor antagonist candesartan (C;2 mg/Kg(-1)/day(-1)) or antihypertensive triple therapy (TT; in mg/Kg(-1)/day(-1);20 hydralazine +7 hydrochlorothiazide +0.15 reserpine) for 10 weeks. Wistar Kyoto rats were used as a normotensive control group. Hypertension was associated with an increase in aortic media area, media-to-lumen ratio and collagen density. Kidneys from SHR showed minimum renal alterations. Aorta and renal gene expression and immunostaining of CTGF were higher in SHR. Candesartan decreased arterial pressure, aortic media area, media-to-lumen ratio and collagen density. However, although arterial pressure decrease was comparable for both treatments, TT partially reduced these parameters. Candesartan-treated rats showed lower levels of vascular CTGF expression, aortic media area, media-to-lumen ratio and collagen density than TT-treated animals. Treatments improve renal damage and reduce renal gene expression and CTGF immunostaining in SHR in a similar manner. The results show that vascular and renal damage is associated with stimulation of CTGF gene and protein content. These results also might suggest that CTGF could be one downstream mediator of Ang II in hypertension-associated organ damage in SHR.
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PMID:Role of connective tissue growth factor in vascular and renal damage associated with hypertension in rats. Interactions with angiotensin II. 1731 87

Type 2 diabetes often occurs in association with hypertension and cardiovascular disease, and markedly increases cardiovascular risk. Strategies to reduce the incidence of diabetes in patients with cardiovascular disease or at high risk for such disease are therefore important. Certain classes of antihypertensive agents, namely the thiazide diuretics and beta-blockers, have an adverse impact on the metabolic profile and increase the risk for new-onset diabetes in hypertensive subjects. In contrast, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), which are blockers of the renin-angiotensin system (RAS), have been shown to increase insulin sensitivity. They may also reduce the risk of diabetes in patients with hypertension or cardiovascular disorders. Some of the evidence in favour of ACE inhibitors and ARBs has come from studies with active comparators that have potential adverse metabolic effects. However, the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) programme demonstrated that the ARB candesartan reduced the incidence of diabetes in heart failure patients in comparison to placebo. The mechanisms responsible for the beneficial effects of RAS blockade remain to be established. Nevertheless, a treatment that can control hypertension and reduce the risk of onset of type 2 diabetes at the same time is certainly desirable.
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PMID:Renin-angiotensin-system blockade in the prevention of diabetes. 1732 Sep 99


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