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

In the last 30 years we have seen considerable progress in the management of patients with diabetes, in particular with diabetic renal disease. A number of paradigms have been broken down, namely the following, as a consequence, clinical care has improved dramatically. . Significant renal involvement and albuminuria is rare in patients with essential hypertension. 2. High GFR is good for prognosis. 3. Only proteinuric diabetic patients have a poor prognosis. 4. Microalbuminuria only predicts renal disease. 5. Reducing blood pressure may cause low perfusion in the kidney and other organs with long-term negative effect, especially on the glomerular filtration rate. 6. Only in the presence of high blood pressure, should microalbuminuric patients receive anti-hypertensive treatment, including blockade of the RAS. 7. Only reducing blood pressure by blocking RAS in diabetes is relevant and justified. 8. Normoalbuminuria as indicated in the present definition is 'normal'. 9. ACE-I or ARB can only be used separately. 10. Diastolic blood pressure and later systolic pulse pressure are the best parameters for blood pressure recording. 11. Microalbuminuria is the strongest risk marker in patients with type 1 diabetes. 12. Screening for microalbuminuria is relevant, but follow-up was not proposed (also regarding microalbuminuria). In the present situation, it is well-known that patients with essential hypertension may sometimes have microalbuminuria, and it is known that it predicts a poor prognosis. Interestingly, in type 1 diabetes, hyperfiltration is a marker for poor prognosis related to metabolic control. Thus hyperfiltration is a marker for bad development, but microalbuminuria (below the proteinuric level) is also associated with a poor prognosis. It was originally believed that microalbuminuria only predicts renal disease. However, surprisingly it predicts as well cardiovascular disease and early mortality. The story about blood pressure and progression of renal disease is interesting, because it was earlier believed that a certain high blood pressure was mandatory for preservation of the renal function. This appeared to be a completely wrong concept. The data regarding microalbuminuria suggest that patients with microalbuminuria should receive anti-hypertensive treatment, even patients with so-called normal blood pressure. This was confirmed in several trials and also included in the guidelines. Reducing blood pressure is important, but it appeared to be especially beneficial to block the renin-angiontensin system, and it is clear that albuminuria is a continuous variable and is also a risk factor. Earlier it was suggested to use ACE-inhibitors or ARBs. Now it is clear that it is possible to use a combination, with good theoretical background. In the history of hypertension, it was earlier believed that diastolic blood pressure was most important, but later on it was generally accepted that systolic is a better predictor and the goal for treatment and pulse pressure may be even better. Not only is microalbuminuria an important risk marker, but it is as well clear that regression of microalbuminuria is a good marker for a better prognosis in patients. Microalbuminuria is believed to be the strongest risk factor, but new studies actually suggest that a simple parameter such as self-rated health is crucial along with other factors. Regarding new developments, it is clear that new studies have led to several advancements in management in patients, for instance the Steno II study shows positive effect on mortality by multifactorial intervention. Similarly, the ADVANCE study also showed positive effect on mortality by more intensified anti-hypertensive treatment with an ACE-inhibitor. We are eagerly awaiting the results from glucose arm in the ADVANCE study, especially in the light of the ACCORD study showing increased mortality with too strict glycemic control with a goal of 6% in HbA1c.
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PMID:Twelve shifting paradigms in diabetic renal disease and hypertension. 1894 97

Angiotensin II AT(1) receptor blockers (ARBs) are commonly used in the clinical treatment of hypertension. Subcutaneous or oral administration of the ARB candesartan inhibits brain as well as peripheral AT(1) receptors, indicating transport across the blood-brain barrier. Pretreatment with candesartan profoundly modifies the response to stress. The ARB prevents the peripheral and central sympathetic activation characteristic of isolation stress and abolishes the activation of the hypothalamic-pituitary-adrenal axis during isolation. In addition, candesartan prevents the isolation-induced decrease in cortical corticotropin-releasing factor 1 and benzodiazepine receptors induced by isolation. When administered before cold-restraint stress, candesartan totally prevents the production of gastric ulcerations. This preventive effect of candesartan is the consequence of profound anti-inflammatory effects, reduction of sympathetic stimulation, and preservation of blood flow to the gastric mucosa. The ARB does not reduce the hypothalamic-pituitary-adrenal axis stimulation during cold restraint. Preservation of the effects of endogenous glucocorticoids is essential for protection of the gastric mucosa during cold restraint. Administration of the ARB to nonstressed rats decreases anxiety in the elevated plus-maze. Our results demonstrate that Angiotensin II, through AT(1) receptor stimulation, is a major stress hormone, and that ARBs, in addition to their antihypertensive effects, may be considered for the treatment of stress-related disorders.
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PMID:Peripherally administered angiotensin II AT1 receptor antagonists are anti-stress compounds in vivo. 1912 Jan 29

Insulin activation of the phosphatidylinositol 3-kinase (PI3K) pathway stimulates glucose uptake in peripheral tissues and synthesis of nitric oxide (NO) in the endothelium. Insulin resistance (IR) and hypertension frequently coexist, particularly among individuals with salt-sensitive hypertension. The mechanisms underlying this association are poorly understood. We investigated these mechanisms in a model of salt-sensitive hypertension in which we have previously shown that endothelial dysfunction is mediated by superoxide anion (O(2)(-)) linked to local ANG II. Dahl salt-sensitive rats were fed, for 6 wk, a normal salt diet (NS; 0.5% NaCl), high-salt diet (HS; 4% NaCl), HS plus the ANG II type 1 receptor (AT(1)R) blocker (ARB) candesartan (10 mg.kg(-1).day(-1)), or HS plus the antioxidant tempol (172 mg/l in drinking water). Hypertensive (mean arterial pressure: 145 +/- 4 vs. 102 +/- 5 mmHg in NS, P < 0.05) rats manifested increased aortic AT(1)R mRNA (210%) and protein (101%) expression and O(2)(-) production (104%) and impaired endothelium-dependent relaxation (EDR) to acetylcholine [maximal response (E(max)): 68 +/- 9 vs. 91 +/- 8% in NS, P < 0.05]. ARB or tempol normalized O(2)(-) and EDR despite that they did not normalize mean arterial pressure, which was reduced only 25%. Hypertensive rats manifested metabolic IR (36% reduction in the glucose infusion rate by insulin clamp), impaired NO-mediated insulin-induced EDR (E(max): 12 +/- 5 vs. 32 +/- 4% in NS, P < 0.05), and impaired insulin activation of PI3K/endothelial NO synthase. ARB or tempol improved insulin-mediated EDR, PI3K, Akt/ endothelial NO synthase phosphorylation, and metabolic IR (all P < 0.05). This study provides insight into the mechanisms that underlie the association between metabolic and hypertensive cardiovascular diseases and support the notion that O(2)(-) overproduction linked to tissue ANG II interferes with shared insulin signaling pathways in metabolic and cardiovascular tissues.
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PMID:Role of angiotensin II and oxidative stress in vascular insulin resistance linked to hypertension. 1915 Dec 53

ANG II AT(1) receptor blockade reduces inflammation in hypertension. To determine whether ANG II AT(1) receptor blockers (ARBs) influence the innate immune inflammatory response in normotensive rats, we studied rat plasma and spleen after a 3-day subcutaneous pretreatment with the ARB candesartan followed by a single dose of the bacterial endotoxin LPS (50 microg/kg ip). Peripheral administration of LPS to rodents produced a generalized inflammatory response with increased release of TNF-alpha, IL-1beta, and IL-6 into the circulation. Candesartan pretreatment reduced the LPS-induced release of TNF-alpha, IL-1beta, and IL-6 into the circulation. The red pulp of rat spleen expressed large numbers of AT(1) receptors and the LPS receptors Toll-like receptor 4 and CD14. Candesartan administration significantly blocked AT(1) receptors. The ARB reduced the LPS-induced upregulation of CD14 gene expression; expression of TNF-alpha and IL-6 mRNA and protein; expression of IL-1beta and IkappaB-alpha mRNA; COX-2 mRNA and protein expression and PGE(2) concentration; inducible nitric oxide synthase (iNOS) gene and protein expression and iNOS activity; and Nox2 gene expression and 8-isoprostane levels. In addition, candesartan reduced the CD14 protein expression in saline- and LPS-treated rats. Our results suggest that AT(1) receptors are essential for the development of the full innate immune response to bacterial endotoxin. The ARB decreased the general peripheral inflammatory reaction to LPS and partially decreased the inflammatory response in the spleen. An unrestricted innate immune response to the bacterial endotoxin may have deleterious effects for the organism and may lead to development of chronic inflammatory disease. We postulate that ARBs may have therapeutic effects on inflammatory conditions.
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PMID:Angiotensin II AT1 blockade reduces the lipopolysaccharide-induced innate immune response in rat spleen. 1922 44

The CORD trials tested ramipril and losartan in patients with hypertension. CORD A randomised 4016 patients with blood pressure (BP) <160/100 mm Hg, who had been treated with an ACEI for >3 months. The patients discontinued ACEI and switched to losartan. After 1 month the BP decreased to 7.7/4.7 mm Hg (p<0.001) and after 1 year to 13.8/8.7 mm Hg (p<0.001). CORD B compared ramipril and losartan in 3813 patients with hypertension who were not being treated with an ACEI or ARB. The patients were randomised to ramipril (n=1926) or losartan (n=1887). After 1 year the BP decreased in the ramipril group to 21.8/13.7 mm Hg (p<0.001) and in the losartan group to 22.0/13.3 mm Hg (p<0.001). No significant differences were found between the groups. No differences were in serious adverse events. Dry cough was more frequently after ramipril (33 vs 4, p<0.001).
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PMID:CORD: COmparison of Recommended Doses of ace inhibitors and angiotensin II receptor blockers. 1929 39

Treatment resistant hypertension is defined as a blood pressure not achieving a goal blood pressure (< 140/90 mm Hg). The diagnosis of resistant hypertension requires use of good blood pressure technique to confirm persistently elevated blood pressure levels. Pseudoresistance, including lack of blood pressure control secondary to poor medication adherence or white coat hypertension, must be excluded. The evaluation of patients with resistant hypertension is focused on identifying contributing and secondary causes of hypertension which are guided by the clinical feature of hypertension: metabolic (obstructive sleep apnea, kidney disease), vascular (renal artery atheroma stenosis), endocrine (hyperaldosteronism), familial (renal artery fibrodyspalsia, adrenal causes). Treatment includes removal of contributing factors, appropriate management of secondary causes, and use of effective multidrug regimens. Three antihypertensive medications including ARB or ACEI in addition to calcium channel blocker and to thiazide diuretics is able to control 75% of hypertensive subjects when prescribed in effective doses. The addition of low dose spironolactone to this triple treatment induces significant BP reduction in most patients with resistant hypertension.
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PMID:[Resistant hypertension: evaluation and treatment]. 1929 24

About 10 years have passed, since the first angiotensin receptor antagonist (ARB), losartan became commercially available in Japan. Six brands of ARB are now available. The excellent effects of ARBs have been demonstrated in recent large-scaled clinical trials such as CASE-J study, Jikei Heart study, HIJ-CREATE study etc. In these studies it was demonstrated that ARBs have moderate antihypertensive effects and pleiotropic actions beyond blood pressure reduction and furthermore ARBs show few side effects compared to other antihypertensive drugs. According to these excellent characteristics of ARBs, ARBs occupied the most important position in the treatment of hypertension. It is supposed that the increasing usage of ARBs will prolong the life span of Japanese people much more in future.
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PMID:[The contribution of ARB to medical treatment]. 1934 25

Diabetes is one of the most important risk factors for mortality along with hypertension. Recently, it has emerged that ARB is a suitable anti-hypertensive drug for diabetic patients, because ARB has some features to prevent the progression of atherosclerosis in diabetic patients. Here, we summarize the evidences suggesting that ARB couldprevent not only macroangiopathy but also microangiopathy in diabetic patients. We conclude that ARB might be an ideal anti-hypertensive drug for diabetic patients.
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PMID:[ARB as a drug for diabetic microangiopathy]. 1934 42

Losartan/hydrochlorothiazide (HCTZ) [Hyzaar(R)] is a fixed-dose combination of the angiotensin II receptor antagonist (angiotensin receptor blocker [ARB]) losartan and the thiazide diuretic HCTZ. It is indicated for the treatment of hypertension (including as initial therapy in severe hypertension) and for stroke risk reduction in patients with hypertension and left ventricular hypertrophy (LVH). Losartan/HCTZ is an effective combination therapy, lowering blood pressure (BP) to a greater extent than losartan or HCTZ alone in patients with hypertension. Other ARB/HCTZ fixed-dose combinations generally lowered BP to a greater extent than losartan/HCTZ in patients with hypertension, although whether this translates into improvements in cardiovascular outcomes is not known. In the LIFE study, losartan-based therapy was associated with a lower incidence of cardiovascular morbidity and mortality than atenolol-based therapy, mainly as a result of a reduced risk of stroke; the incidence of new-onset diabetes mellitus was also lower with losartan-based therapy. Losartan/HCTZ is a well tolerated combination therapy. Thus, losartan/HCTZ remains an important option in the treatment of hypertension, as well as being indicated to reduce stroke risk in patients with hypertension and LVH.
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PMID:Losartan/Hydrochlorothiazide: a review of its use in the treatment of hypertension and for stroke risk reduction in patients with hypertension and left ventricular hypertrophy. 1953 40

A number of previous investigators have demonstrated that arterial augmentation index (AIx), a measure of apparent arterial stiffness, reflects in part vascular endothelial function, and that AIx is modulated by nitric oxide (NO) responses. We evaluated AIx in a population of 253 ageing subjects (mean age 63.4+/-6 (standard deviation, SD) years) and its relationship to (i) plasma levels of asymmetric dimethylarginine (ADMA), a marker and mediator of vascular endothelial dysfunction and (ii) the ratio of ADMA to its non-metabolised enantiomer symmetric dimethylarginine (SDMA), an inverse index of ADMA metabolic clearance. Evaluation was performed by univariate followed by multivariate analyses. On multivariate analyses, both ADMA (beta=0.16, p=0.01) and ADMA:SDMA (beta=0.21, p<0.001) ratio were significant direct correlates of AIx. Other significant correlates of AIx on multivariate analysis were: use of angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (ACEi/ARB) (beta=-0.24, p=0.004), smoking history (beta=0.15, p=0.007), male gender (beta=-0.38, p<0.001), creatinine clearance (CrCL) (beta=-0.25, p<0.001), and history of hypertension (beta=0.17, p=0.04). We conclude that (1) endothelial dysfunction engendered by impairment of NO synthesis may represent the basis for increased arterial stiffness in ageing individuals and (2) the fundamental biochemical anomaly may be impairment of ADMA clearance. These pathophysiological factors are likely to be relevant to optimize therapy to ameliorate disorders of arterial compliance in the ageing population.
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PMID:Correlates of arterial stiffness in an ageing population: role of asymmetric dimethylarginine. 1955 93


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