Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin II receptor blockers (ARBs) are widely used for the treatment of hypertension. It is believed that treatment with an ARB increases the level of plasma angiotensin II (Ang II) because of a lack of negative feedback on renin activity. However, Ichikawa (Hypertens Res 2001; 24: 641-646) reported that long-term treatment of hypertensive patients with olmesartan resulted in a reduction in plasma Ang II level, though the mechanism was not determined. It has been reported that angiotensin 1-7 (Ang-(1-7)) potentiates the effect of bradykinin and acts as an angiotensin-converting enzyme (ACE) inhibitor. It is known that ACE2, which was discovered as a novel ACE-related carboxypeptidase in 2000, hydrolyzes Ang I to Ang-(1-9) and also Ang II to Ang-(1-7). It has recently been reported that olmesartan increases plasma Ang-(1-7) through an increase in ACE2 expression in rats with myocardial infarction. We hypothesized that over-expression of ACE2 may be related to a reduction in Ang II level and the cardioprotective effect of olmesartan. Administration of 0.5 mg/kg/day of olmesartan for 4 weeks to 12-week-old stroke-prone spontaneously hypertensive rats (SHRSP) significantly reduced blood pressure and left ventricular weight compared to those in SHRSP given a vehicle. Co-administration of olmesartan and (D-Ala7)-Ang-(1-7), a selective Ang-(1-7) antagonist, partially inhibited the effect of olmesartan on blood pressure and left ventricular weight. Interestingly, co-administration of (D-Ala7)-Ang-(1-7) with olmesartan significantly increased the plasma Ang II level (453.2+/-113.8 pg/ml) compared to olmesartan alone (144.9+/-27.0 pg/ml, p<0.05). Moreover, olmesartan significantly increased the cardiac ACE2 expression level compared to that in Wistar Kyoto rats and SHRSP treated with a vehicle. Olmesartan significantly improved cardiovascular remodeling and cardiac nitrite/ nitrate content, but co-administration of olmesartan and (D-Ala7)-Ang-(1-7) partially reversed this anti-remodeling effect and the increase in nitrite/nitrate. These findings suggest that olmesartan may exhibit an ACE inhibitory action in addition to an Ang II receptor blocking action, prevent an increase in Ang II level, and protect cardiovascular remodeling through an increase in cardiac nitric oxide production and endogenous Ang-(1-7) via over-expression of ACE2.
 ...
PMID:Olmesartan is an angiotensin II receptor blocker with an inhibitory effect on angiotensin-converting enzyme. 1734 82

Angiotensin II receptor blockers (ARBs) are widely used in patients with hypertension, heart failure, diabetic nephropathy, and other conditions. Over-stimulation of AT2 receptor as a result of AT1 blockade may contribute to the beneficial effects of ARBs through vasodilation and inhibition of cardiac and vascular hypertrophy and fibrosis. Some experimental studies, however, suggested that AT, receptor overstimulation, in addition to beneficial effects, might trigger inhibition of angiogenesis and apoptosis. In a review, some authors suggested that ARBs may increase the risk of myocardial infarction. This position triggered a hot scientific debate and further analyses of existing data. We completed a meta-analysis of randomized clinical trials comparing ARBs with either placebo or active drugs different from ARBs. ARBs were not associated with an excess risk of myocardial infarction (odds ratio 1.03 in a random-effect model and 1.02 in a fixed-effect model). Cardiovascular mortality did not differ between ARBs and drugs different from ARBs (odds ratio 1.00 in a random-effect model and 0.99 in a fixed-effect model) and it was slightly lesser with ARBs than with placebo (odds ratio 0.91; 95% confidence interval 0.83-0.99; p = 0.042) in a prespecified subgroup analysis. Other meta-analyses confirmed these data. In conclusion, evidence from randomized trials does not support the hypothesis that AT2 receptor over-stimulation produces harmful clinical effects. Current indications and contraindications to the use of ARBs in patients with hypertension, heart failure, and diabetic nephropathy should be maintained and probably extended to the entire class of these drugs.
 ...
PMID:[Antihypertensive therapy and cardiovascular prevention. The role of angiotensin II receptor blockers]. 1769

The metabolic syndrome (MS), a cluster of risk factors, such as obesity, hyperglycemia, hypertension and dyslipidemia, contributes to the development of cardio-vascular diseases and type 2 diabetes mellitus (DM2). Insulin resistance (IR) plays a key role in MS being strongly linked to abdominal visceral fat. Treatment for obese patients with MS should aim at improving IR, delaying the onset of DM2 and at reducing cardio-vascular risk. Weight loss, first therapeutic target, may be obtained through life-style modifications and anti-obesity drugs or bariatric surgery, at need. In these patients drug therapy is necessary if therapeutic life-style changes are not sufficient. Some drugs have adverse metabolic effects, therefore the therapeutic choices must be specific and rational. Metformin, Thiazolidinediones and Acarbose are anti-hyperglycemic drugs of choice: they reduce the incidence of DM2 and IR (or improve insulin sensitivity) and they decrease or stabilize the visceral adipose tissue mass (Thiazolidinediones increases subcutaneous fat only). Also Angiotensin II receptor blockers and Angiotensin-converting enzyme inhibitors reduce the incidence of DM2 and insulin resistance and they are first-line antihypertensive drugs in MS. Calcium channel blockers, Alpha-1 antagonists and Alpha-2 agonists drugs are metabolically neutral and slight weight gains are related to the hydro-sodium retention. Beta-blockers and Diuretics, except for Indapamide and Anti-aldosterone drugs, can reduce insulin sensitivity, impair lipid profile and increase DM2 incidence; they are not first-line therapy yet they are necessary in selected cases only. Statins, Fibrates and omega-3 Fatty acids are indicated to normalize dyslipidemia. Low doses of acetylsalicylic acid are also recommended.
 ...
PMID:[Therapeutic options for metabolic syndrome in obese patients]. 1806 54

The renin-angiotensin-aldosterone system (RAAS) plays a crucial role in blood pressure regulation and hypertension-related complications. Angiotensin-converting enzyme inhibitors (ACEIs) were the first to be used to block the RAAS and now have many compelling indications in the treatment of hypertension and its cardiovascular and renal complications. Angiotensin II receptor blockers (ARBs), introduced 20 years later, have been shown to be equally as effective as antihypertensive treatment and are also associated with a lower number of side effects. Furthermore, in clinical trials ARBs and ACEIs were associated with comparable benefits for their most typical indications. This was confirmed in the 2007 New European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines for the management of hypertension by comparable specific recommendations for ARB and ACEI treatment. There is sufficient theoretical background and, in some cases, also clinical evidence that combination therapy with ACEIs and ARBs may be more beneficial than monotherapy with either of the groups alone, both in uncomplicated hypertension and with concomitant heart failure or renal dysfunction. However, the combination of ACEI and ARB was not recommended in the ESH/ESC 2007 Guidelines. This may change after the publication of the Ongoing Telmisartan Alone and in Combination with Ramipril Global End point Trial (ONTARGET) study, the preliminary results of which have just been presented. In heart failure, recent studies have shown that the combination of ACEI and ARB decreases cardiovascular mortality and the number of hospitalizations due to aggravation of heart failure. These results have been reflected in the newest ESC guidelines of the heart failure treatment. Nephroprotective properties of the combination of ACEs and ARBs have been proved both in studies on nondiabetic and diabetic nephropathy. The potential benefits, indications in prespecified groups of patients, the most recent data from clinical trials and latest research regarding dual blockade of RAAS will be reviewed in this article.
 ...
PMID:Current possibilities of ACE inhibitor and ARB combination in arterial hypertension and its complications. 1851 Apr 91

Recent evidence suggests a coordinated regulation by the local renin-angiotensin system (RAS) and tissue kallikrein-kinin system (TKKS) of blood flow and substrate supply in oxidative red myofibres of skeletal muscle tissue during endurance exercise. The performance of these myofibres is dependent on the increased oxidation of substrates facilitated by augmenting nutritive blood flow and glucose uptake. Humoral factors released by the contracting fibres, such as adenosine and kinins, are suggested to be responsible for this metabolic adjustment. The considerable drain of blood volume and the enormous consumption of glucose during endurance exercise require a control mechanism for the maintenance of blood pressure (BP) and glucose homeostasis. This is achieved by the sympathetic nervous system and its subordinate RAS, which is located in the nutritive vessels and parenchyma of the red myofibres. The angiotensin-converting enzyme (ACE) is the primary enzyme responsible for kinin degradation during exercise, underscoring the important interrelationship between the RAS and the TKKS in the critical role of kinins in the multifactorial regulation of muscle bioenergetics and glucose and BP homeostasis. Importantly, overactivity of the ACE, as occurs in individuals displaying risk factors such as overweight, causes exaggerated BP response and reduced glucose disposal. If they persist over years, compensatory responses to this ACE overactivity, such as hypersecretion of insulin and compliance of the vessel walls, will inevitably be exhausted, leading ultimately to the manifestation of type 2 diabetes and hypertension. This concept also provides a unifying explanation for the beneficial effects of ACE-inhibitors and Angiotensin II receptor antagonists in the treatment of hypertension and insulin resistance.
 ...
PMID:Angiotensin-converting enzyme in skeletal muscle: sentinel of blood pressure control and glucose homeostasis. 1858 83

Hypertension is an important risk factor for cardiovascular disease (CVD), particularly in patients with comorbid obesity, diabetes, metabolic disease, or end-organ damage. An integrated CV risk management approach is being adopted: aggressive blood pressure (BP) control is important in patients with high CVD risk, and well-tolerated antihypertensive agents with protective benefits beyond BP lowering are advantageous. The renin-angiotensin system is integral to blood pressure control and is well established in the pathophysiology of CVD. Angiotensin II receptor blockers (ARBs) are highly efficacious, persistent, well-tolerated antihypertensive agents, with additional benefits in comorbid hypertension, CV pathologies, end-organ damage, and, in diabetes, diabetic nephropathy or metabolic syndrome. ARBs decrease overall risk of CV and end-organ disease, CVD-related mortality, and cerebrovascular events in patients with hypertension.
 ...
PMID:The importance of integrated risk management when treating patients with hypertension: benefits of angiotensin II receptor antagonist therapy. 1863 62

The Angiotensin II receptor blockers (ARBs) have been efficacious and safe drugs for the treatment of hypertension, heart failure, diabetic nephropathy and stroke from several short and long term clinical trials. The ARBs exert their effects through selective blockade of the angiotensin II (Ang-II) subtype 1 (AT1) receptor and quite possibly through stimulation by Ang-II of the unoccupied subtype 2 (AT2) receptor. The ARBs are equipotent to other antihypertensive drugs with respect to their effect on blood pressure, heart failure or diabetic nephropathy. They appear to be superior to the other drugs with respect to their stroke protective effect. They exert their stroke protective effect by a dual action, selectively blocking the action of Ang-II on the AT1 receptors, while allowing Ang-II to stimulate the unoccupied AT2 receptors. This dual action is unique to ARBs and results in vasodilation and increase in blood flow to the ischemic zone of the brain leading to improvement and prevention of its extension. All these actions of the ARBs will be discussed in this comprehensive review.
 ...
PMID:Clinical experience with the use of angiotensin receptor blockers in patients with cardiovascular, cerebrovascular and renal diseases. 1866 66

Angiotensin II receptor blockers (ARBs) are widely used in patients with hypertension, heart failure and type 2 diabetes mellitus (T2DM). Several large clinical trials have demonstrated that these agents are effective in reducing cardiovascular mortality and morbidity. These benefits are partly independent of the degree of blood pressure reduction and most likely related to ARBs' anti-inflammatory, metabolic and vascular effects. Clinical studies showed that the anti-inflammatory effect of ARBs could be related to the dosage and/or the length of the treatment. In large clinical trials, ARBs have inconsistently reduced the risk of new-onset T2DM. Among ARBs, only losartan significantly reduced serum uric acid levels. Moreover, it has been demonstrated that ARBs improve endothelial dysfunction in patients with hypertension and/or coronary artery disease (CAD), while all but one of the studies proved that these agents could usually, after 6-12 months of therapy, induce regression of vascular hypertrophy in hypertensive patients. These positive effects could be relevant to vascular protection and, together with the blood pressure reduction, constitute the background of the improved outcome observed in clinical studies on mortality and/or morbidity in hypertensive, high-risk and CAD patients. The clinical significance of the different potency of ARBs needs to be investigated further in specific and adequately powered trials.
 ...
PMID:Vascular and metabolic effects of angiotensin II receptor blockers. 1923 92

Candesartan cilexetil is one of a number of drugs of the angiotensin II receptor blocker (ARB) class. Their principal mode of action involves competitive blockade of the angiotensin II type 1 receptor, thereby modulating the activity of the rennin-angiotensin-aldosterone system. Angiotensin II receptor blocker therapy has been proven to be well tolerated and effective in the management of hypertension, chronic heart failure with left ventricular dysfunction and the prevention and progression of diabetic renal disease. Candesartan is a highly potent, long-acting and selective angiotensin II type 1 receptor blocker. It was launched in 1998 for the treatment of hypertension. Its use has increased dramatically, with recently published data suggesting benefit in the treatment of stroke, heart failure, diabetic renal disease and most recently in preventing the development of or delaying the progression of diabetic retinopathy. In this article we review the literature on the use of ARB drugs in general before focusing on candesartan.
 ...
PMID:Candesartan: widening indications for this angiotensin II receptor blocker? 1956 75

Patients with chronic kidney disease progress to end stage renal disease and about 86% are diagnosed hypertensives. Hypertension is a risk factor for cardiovascular disease which is the main cause of morbidity and mortality in the dialysis population. Pre and post-dialysis blood pressure values of <140/90 mmHg are recommended as the optimal blood pressure. The extra-cellular volume (ECV) expansion is the main pathophysiological determinant of hypertension in dialysis patients. The efforts should be made to correctly estimate and achieve the patients dry body weigh and to limit dietary sodium intake. Angiotensin II receptor antagonists, beta blockers and calcium channel blockers are recommended as first choice drugs. Beta blockers and calcium channel blockers have been associated with reduced cardiovascular mortality and give their protective effects in patients at high risk. Antihypertensive drug therapies can effectively reduce blood pressure and are needed by the vast majority of hemodialysis patients.
 ...
PMID:The management of hypertension in hemodialysis and CAPD patients. 1958 88


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>