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

There is no question about the contributory risk of hypertension in morbidity and mortality from cardiovascular (CV) disease and chronic kidney disease (CKD). Another independent risk factor for CV disease and CKD is proteinuria, which is most commonly caused by dysfunction of the kidney glomerular filter, in particular of the podocyte. Podocytes are highly differentiated pericyte-like cells that are essential to normal kidney function. Moreover, loss of podocytes is a hallmark of diabetic and nondiabetic progressive CKD. Recent data point to an important role for the renin-angiotensin system (RAS) and calcium signaling in the structural and functional integrity of podocytes. Given this scenario, it is desirable to treat hypertension with agents targeting the RAS, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin II (Ang II) type 1-receptor blockers (ARB). These agents have proven effects on lowering blood pressure (BP) and can reduce podocyte injury. Here we review the dual effects of RAS blockade on BP and on podocyte function and emphasize BP-dependent and BP-independent effects of this regimen.
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PMID:Dual effects of RAS blockade on blood pressure and podocyte function. 1817 88

Diabetic nephropathy is a major cause of end-stage renal failure (ESRF) in patients with both type 1 and type 2 diabetes. Many factors such as genetic and non-genetic promoters, hypertension, hyperglycemia, accumulation of advanced glycation end products (AGEs), dyslipidemia, albuminuria and proteinuria influence the progression of this disease. It is important to determine pathogenesis and treatment of this disease. However, it is difficult to investigate since human diabetes is a heterogeneous and multifactorial disease. Therefore, most of these mechanisms have been investigated in animal experiments. KK/Ta mice have a clearly different genetic background in terms of body weight, blood glucose, impaired glucose tolerance (IGT), urinary albumin excretion and serum triglyceride than BALB/c mice. Renal lesions of KK/Ta mice closely resemble those in human early diabetic nephropathy. Thus, the KK/Ta mouse may serve as a suitable model for the study of type 2 diabetes and early diabetic nephropathy in humans. We reviewed genetic susceptibility using genome-wide linkage analysis and differential display polymerase chain reaction (DD-PCR) or Northern blot analysis, and treatment of diabetic nephropathy using angiotensin type 1 (AT1) receptor blockers (ARB) or thiazolidinediones (TZDs) in KK/Ta mice.
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PMID:Pathogenesis and treatment of type 2 diabetic nephropathy: lessons from the spontaneous KK/Ta mouse model. 1822 Jun 4

We evaluated the effects of the angiotensin II (Ang II) receptor blocker (ARB) losartan on the formation and number of endothelial progenitor cells (EPCs) in hypertensive rats. Wistar-Kyoto (WKY) rats and stroke-prone, spontaneously hypertensive rats (SHR-SP) were salt-loaded and then treated with losartan (10 mg/kg/day), trichlormethiazide (TCM; 1.6 mg/kg/day), or tempol (1 mmol/L) for 2 weeks. Peripheral blood mononuclear cells were isolated, subjected to flow cytometric analysis to determine the number of circulating EPCs, cultured to assay EPC colony formation, and subjected to a migration chamber assay to evaluate EPC migration. Oxidative stress in EPCs was evaluated by thiobarbituric acid reactive substance (TBARS) assay. The results showed that the number, colony formation, and migration of EPCs were markedly decreased in SHR-SP compared to those in WKY rats. The TBARS scores were significantly greater in SHR-SP than in WKY rats. Losartan and TCM decreased systolic blood pressure in SHR-SP to similar levels. Losartan and tempol increased the number of circulating EPCs and colony formation, and inhibited oxidation in SHR-SP. TCM did not affect the EPC number, colony formation, or oxidation. Both losartan and TCM stimulated EPC migration. Expression of gp91(phox), p22(phox), and p47(phox) mRNA in tissues was significantly decreased by losartan but not by TCM. These results indicate that the formation and function of EPCs are impaired by oxidative stress in SHR-SP. This is the first report to show that losartan improves the proliferation and function of EPCs in hypertension, suggesting that ARBs are useful to repair hypertensive vascular injuries.
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PMID:Losartan improves the impaired function of endothelial progenitor cells in hypertension via an antioxidant effect. 1825 May 49

The development of aliskiren, the first orally effective renin inhibitor, utilized molecular modeling based upon X-ray crystallographic analysis of renin's active site to design a potent, low molecular weight renin inhibitor with improved bioavailability (approximately 2.6%). In patients with hypertension, dose-dependent BP reduction occurs with aliskiren 75-300 mg once daily; at these doses, the safety and tolerability profile is comparable to placebo. In direct comparison studies, BP reduction with aliskiren is equivalent to commonly used antihypertensive agents including diuretics, ACE inhibitors, and ARBs. Persistent BP reduction and prolonged suppression of plasma renin activity (PRA) is observed after aliskiren withdrawal. Aliskiren suppresses PRA when given either as monotherapy or in combination with other agents. When added to an ARB, aliskiren blocks compensatory RAS activation and produces significant additional BP reduction. In patients with diabetic nephropathy, addition of aliskiren to losartan, 100 mg resulted in a 20% greater reduction in proteinuria. Ongoing studies evaluating the long-term renal protective effects of aliskiren and its effects on ventricular remodeling are currently planned or underway.
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PMID:Current concepts: renin inhibition in the treatment of hypertension. 1830 34

The benefit of prescribing angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-II receptor antagonists (ARB) to kidney transplant recipients remains controversial. We investigated determinants and prescribing patterns of ACEi/ARB during the first year following kidney transplantation. All recipients of a first kidney transplant performed at the university hospital of Nancy (France) between January 1997 and June 2004 were included. Determinants of ACEi/ARB prescription were identified by Cox models among various recipient characteristics (at transplantation and during follow-up), donor characteristics and transplant parameters. Of 491 patients, 28.9% started using ACEi/ARB during the year after transplantation, and 26.9% were taking them at one yr. Recipient determinants of ACEi/ARB use were male sex (HR: 1.82, p = 0.003), pre-transplant hypertension (HR: 2.27, p = 0.0002) and ACEi/ARB administration (HR: 1.85, p = 0.002), post-transplant proteinuria (HR: 1.62, p < 0.0001) and anemia (HR: 4.08, p < 0.0001). Glomerular filtration rate level was not associated with ACEi/ARB use. Post-transplant hypercholesterolemia (HR: 0.42, p = 0.013) and higher donor age (HR: 0.98, p = 0.015) were associated with a lower likelihood of ACEi/ARB use. Fewer HLA mismatches (HR: 1.16, p = 0.029) and shorter cold ischemia duration (HR: 1.02, p = 0.045) were also independent predictors of ACEi/ARB use. Regardless of recipient characteristics, nephrologists were more likely to prescribe ACEi/ARB after kidney transplantation when the transplant parameters were favorable.
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PMID:Determinants and patterns of renin-angiotensin system inhibitors' prescription in the first year following kidney transplantation. 1831 41

Hypertension is one of the leading risk factors for cardiovascular disease and represents a major health and economic burden. Most patients with high- or very high-risk hypertension have multiple cardiovascular risk factors with or without accompanying subclinical organ damage or established cardiovascular or renal disease. Patients with severe hypertension or with moderate hypertension and one to two additional risk factors have absolute 10-year risks of cardiovascular disease of 21-30% and 15-20%, respectively. Current European treatment guidelines recommend that antihypertensive therapy be initiated rapidly and aggressively in patients with high-risk hypertension. Most patients require two or more antihypertensive agents to achieve the strict blood pressure target of <130/80 mmHg. This article reviews the existing cost-effectiveness data on the use of angiotensin II receptor antagonists (blockers) [ARBs] in patients with high-risk hypertension. Aggressive ARB treatment of patients in the early (microalbuminuric) stages of diabetic nephropathy has a significant renoprotective effect, delaying the onset of overt (proteinuric) nephropathy. By slowing the progression of these patients to end-stage renal disease, substantial cost savings can be made. There is a paucity of cost-effectiveness data regarding the use of fixed-dose ARB plus thiazide diuretic combination therapies. Longitudinal cost-benefit studies of this attractive and efficacious first-line treatment option are needed.
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PMID:Economic benefits of treating high-risk hypertension with angiotensin II receptor antagonists (blockers). 1834 11

Pharmacological treatment of hypertension is effective in preventing cardiovascular and renal complications. Calcium antagonists (CAs) and blockers of the renin-angiotensin system [angiotensin-converting enzyme (ACE) inhibitors and angiotensin II antagonists (ARBs)] are widely used today to initiate antihypertensive treatment but, when given as monotherapy, do not suffice in most patients to normalise blood pressure (BP). Combining a CA and either an ACE-inhibitor or an ARB considerably increases the antihypertensive efficacy, but not at the expense of a deterioration of tolerability. Several fixed-dose combinations are available (CA + ACE-inhibitors: amlodipine + benazepril, felodipine + ramipril, verapamil + trandolapril; CA + ARB: amlodipine + valsartan). They are expected not only to improve BP control, but also to facilitate long-term adherence with antihypertensive therapy, thereby providing maximal protection against the cardiovascular and renal damage caused by high BP.
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PMID:Concomitant calcium entry blockade and inhibition of the renin-angiotensin system: a rational and effective means for treating hypertension. 1840 2

New onset diabetes (NOD) is common among hypertensive patients, whether they are being treated for hypertension or not, and is associated with subsequently increased cardiovascular disease (CVD). Thiazide-like diuretics and beta-blockers are more likely to provoke hyperglycemia when compared with drugs that block the renin-angiotensin system, and calcium channel blockers. However, in contrast to the NOD arising during treatment with other antihypertensive drugs, the NOD that occurs during diuretic treatment, has not been shown to increase CVD, either in clinical trials, or during longer observational studies. In fact, blood pressure reduction achieved by diuretic treatment may avert the expected increase of CVD in NOD. Conventional blood pressure reduction (along with lipid lowering) is the proven approach to preventing CVD in diabetes, in whatever circumstances the diabetes occurs. Apprehensions relating to the potential onset of NOD should not influence the choice of the initial antihypertensive treatment choice, nor should it invariably lead to discontinuation of diuretics (although such a step may reverse hyperglycemia). NOD can also sometimes be eliminated by correcting hypokalemia with a potassium-sparing diuretic, and/or potassium supplementation, or by adding a potassium-conserving antihypertensive drug such as an ACEI, ARB, or an anti-aldosterone agent. If all these stratagems fail (or are unsuitable), and the diuretic is essential to blood pressure control, then hypoglycemic therapy is indicated. NOD does adversely affect quality of life, and is not to be accepted lightly. However, diuretic-induced hyperglycemia can be managed, and should be tolerated if a diuretic is essential for blood pressure control. In summary, the potential for occurrence of NOD certainly needs consideration, but it is not an insurmountable challenge, and must not compromise aggressive blood pressure control, which remains the primary tool for antihypertensive care.
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PMID:New onset diabetes during antihypertensive therapy. 1843 39

Several factors have been incriminated in the genesis of diabetic nephropathy. To elucidate their interplay, we have used a hypertensive, obese, diabetic rat model with nephropathy (SHR/NDmcr-cp) that mimics human type 2 diabetes. This model is characterized by hypertension, obesity with the metabolic syndrome, diabetes with insulin resistance, and intrarenal advanced glycation end product (AGE) accumulation. In order to achieve renoprotection, which was evaluated by histology and albuminuria, various therapeutic approaches were used: caloric restriction, antihypertensive agents (angiotensin II receptor blocker [ARB] and calcium channel blocker), lipid- (bezafibrate) or glucose-lowering (insulin and pioglitazone) agents, and cobalt chloride (a hypoxia-inducible factor activator). Altogether, renoprotection is not necessarily associated with blood pressure or glycemic control. By contrast, it is almost always associated with decreased AGE formation, with the exception of insulin, which induces hyperinsulinemia, eventually leading to an overproduction of transforming growth factor-beta. AGE formation is reduced directly by in vitro active compounds (e.g., ARBs) or indirectly by in vitro inactive compounds (e.g., pioglitazone and cobalt). In the latter cases, AGE reduction may reflect a decreased oxidative stress as it is concomitant with a marked reduction of oxidative stress markers. It remains to be seen whether the renoprotection offered by these various approaches may be additive.
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PMID:Inhibition of advanced glycation end products: an implicit goal in clinical medicine for the treatment of diabetic nephropathy? 1844 8

Cardiovascular disease represents a continuum that starts with risk factors such as hypertension and progresses to atherosclerosis, target organ damage, and ultimately to myocardial infarction, heart failure, stroke or death. Renin-angiotensin system (RAS) blockade with angiotensin converting enzyme (ACE) inhibitors or angiotensin AT(1)-receptor blockers (ARBs) has turned out to be beneficial at all stages of this continuum. Both classes of agent can prevent or reverse endothelial dysfunction and atherosclerosis, thereby reducing the risk of cardiovascular events. Such a reduction has been shown mainly for ACE inhibitors in patients with coronary artery disease, but recent studies revealed that ARBs are not inferior in this respect. However, no such data are currently available on the combination of these drugs. Both ACE inhibitors and ARBs have been shown to reduce target organ damage in organs such as the kidney, brain and heart, and to decrease cardiovascular mortality and morbidity in patients with congestive heart failure. Experimental data point to an influence of ACE inhibitors and ARBs on the number and function of endothelial progenitor cells revealing additional mechanisms of action of these drugs. The VALIANT trial has shown equivalent effects of ARB valsartan and the ACE-inhibitor captopril in patients post myocardial infarction, but the dual RAS-blockade, compared to monotherapy, did not further reduce events. In secondary prevention, the most-recently published ONTARGET study provides evidence that on top of a better tolerability AT(1)-receptors antagonists are equal to ACE inhibitors in the prevention of clinical endpoints like cardiovascular mortality and morbidity, myocardial infarction and stroke. The combined RAS blockade, however, achieved no further benefits in vascular high-risk patients and was associated with more adverse events. In chronic heart failure, ValHeFT and CHARM-ADDED have shown that combined RAS inhibition with ACE inhibitor and valsartan or candesartan reduced morbidity and mortality in certain patient subgroups. Accumulating evidence also points to benefits of the combination therapy in individuals with proteinuric nephropathies. In conclusion, while combined RAS-inhibition is not generally indicated in patients along the cardio-reno-vascular continuum, it has already proven to be effective in heart failure patients with incomplete neuroendocrine blockade. In secondary prevention, monotherapy with either RAS inhibitor is equally efficacious. Furthermore, novel pharmacologic agents such as renin inhibitors may prove useful in preventing common side effects of RAS blockade such as angiotensin escape and AT(1)-receptor upregulation, giving clinicians additional therapeutic tools to optimally treat the individual patient.
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PMID:RAS blockade with ARB and ACE inhibitors: current perspective on rationale and patient selection. 1845 36


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