UMLS:C0011849 - FACTA Search

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Query: UMLS:C0011849 (diabetes)
277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The combined effect of diabetes and hypertension on the plasma angiotensin II (AII)/glomerular AII receptor (AII-R) relationship in streptozotocin-induced diabetes was investigated as well as the effect of glycaemic control on this relationship. 2. Diabetes was induced in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats with streptozotocin 60 mg/kg and blood sugars maintained between 18-21 mmol/L (uncontrolled diabetes) and 4-8 mmol/L (controlled diabetes). Rats were killed on days 1 and 7. Angiotensin II receptor was estimated by saturation analysis and plasma AII by radio-immunoassay. 3. Angiotensin II receptors were significantly higher in non-diabetic SHR than WKY rats (708 +/- 62 and 388 +/- 36 fmol/mg protein, respectively, P = 0.0008). Plasma AII were comparable in both groups (47 +/- 2.7, 38 +/- 3.5 pg/mL, respectively) and a significant inverse relationship between AII/AII-R was observed (WKY P = 0.02 and SHR P = 0.004). 4. On day 7, plasma AII and AII-R levels in diabetic groups were comparable with those of their non-diabetic controls. Diabetic WKY rats maintained an inverse correlation between AII and AII-R (controlled P = 0.04 and uncontrolled P = 0.015), but this did not occur in the SHR. 5. Absence of receptor response to varying ligand concentrations in the diabetic SHR may contribute to the development of nephropathy. Glycaemic control does not appear to reverse this abnormality in the SHR, so that co-existent hypertension may have a more direct influence on renal function.
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PMID:Abnormality of the glomerular angiotensin II receptor in experimental diabetic nephropathy. 832 23

Angiotensin II receptor antagonists (AT-1) represent a new group of orally active antihypertensive agents. Activation on AT-1 receptor leads to vasoconstriction, stimulation of the release of catecholamines and antidiuretic hormone with production of thirst, and promote growth of vascular and cardiac muscle; these effects are blocked by AT-1 antagonist agents. The first chemically useful, orally active AT-1 receptor antagonist was losartan, followed by other agents currently in clinical use, such as: valsartan, eprosartan, irbesartan, telmisartan, candesartan, and many others under investigation. AT-1 receptor antagonists are effective in reducing high blood pressure in hypertensive patients. Monotherapy in mild to moderate hypertension controls blood pressure in 40 to 50% of these patients; when a low dose of a thiazide diuretic is added, 60 to 70% of patients are controlled. The efficacy is similar to angiotensin-converting enzyme inhibitors, diuretics, calcium antagonists and beta-blocking agents. Tolerability has been reported to be very good. AT-1 receptor antagonists would be a drug of choice in otherwise well-controlled hypertensive patients treated with angiotensin-converting enzyme inhibitors who developed cough or angioedema. The final position in the antihypertensive therapy in this special population and other clinical situations, such as left ventricular hypertrophy, heart failure, diabetes mellitus and renal disease, has to be determined in large prospective clinical trials, some of which are now being conducted.
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PMID:Angiotensin II receptor antagonists in arterial hypertension. 1085 84

Angiotensin II receptor blockers (ARBs) represent a new class of effective and well tolerated orally active antihypertensive agents. Recent clinical trials have shown the added benefits of ARBs in hypertensive patients (reduction in left ventricular hypertrophy, improvement in diastolic function, decrease in ventricular arrhythmias, reduction in microalbuminuria, and improvement in renal function), and cardioprotective effect in patients with heart failure. Several large long-term studies are in progress to assess the beneficial effects of ARBs on cardiac hypertrophy, renal function, and cardiovascular and cerebrovascular morbidity and mortality in hypertensive patients with or without diabetes mellitus, and the value of these drugs in patients with heart disease and diabetic nephropathy. The ARBs specifically block the interaction of angiotensin II at the AT1 receptor, thereby relaxing smooth muscle, increasing salt and water excretion, reducing plasma volume, and decreasing cellular hypertrophy. These agents exert their blood pressure-lowering effect mainly by reducing peripheral vascular resistance usually without a rise in heart rate. Most of the commercially available ARBs control blood pressure for 24 h after once daily dosing. Sustained efficacy of blood pressure control, without any evidence of tachyphylaxis, has been demonstrated after long-term administration (3 years) of some of the ARBs. The efficacy of ARBs is similar to that of thiazide diuretics, beta-blockers, angiotensin-converting enzyme inhibitors or calcium channel blockers in patients with similar degree of hypertension. Higher daily doses, dietary salt restriction, and concomitant diuretic or ACE inhibitor administration amplify the antihypertensive effect of ARBs. The ARBs have a low incidence of adverse effects (headache, upper respiratory infection, back pain, muscle cramps, fatigue and dizziness), even in the elderly patients. After the approval of losartan, five other ARBs (candesartan cilexetil, eprosartan, irbesartan, telmisartan, and valsartan) and three combinations with hydrochlorothiazide (irbesartan, losartan and valsartan) have been approved as antihypertensive agents, and some 28 compounds are in various stages of development. The ARBs are non-peptide compounds with varied structures; some (candesartan, losartan, irbesartan, and valsartan) have a common tetrazolo-biphenyl structure. Except for irbesartan, all active ARBs have a carboxylic acid group. Candesartan cilexetil is a prodrug, while losartan has a metabolite (EXP3174) which is more active than the parent drug. No other metabolites of ARBs contribute significantly to the antihypertensive effect. The variation in the molecular structure of the ARBs results in differences in the binding affinity to the receptor and pharmacokinetic profiles. The differences observed in lipid solubility, absorption/distribution, plasma protein binding, bioavailability, biotransformation, plasma half-life, and systemic elimination influence the time of onset, duration of action, and efficacy of the ARBs. On the basis of the daily mg dose, the antihypertensive potency of the ARBs follows the sequence: candesartan cilexetil > telmisartan approximately = losartan > irbesartan approximately = valsartan > eprosartan. After oral administration, the ARBs are rapidly absorbed (time for peak plasma levels = 0.5-4 h) but they have a wide range of bioavailability (from a low of 13% for eprosartan to a high of 60-80% for irbesartan); food does not influence the bioavailability, except for valsartan (a reduction of 40-50%) and eprosartan (increase). A limited dose-peak plasma levels/areas under the plasma level-time curve proportionality is observed for some of the ARBs. Most of these drugs have high plasma protein binding (95-100%); irbesartan has the lowest binding among the group (90%). The steady-state volumes of distribution vary from a low of 9 L (candesartan) to a high of 500 L (telmisartan). (ABSTRACT TRUNCATE
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PMID:Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension. 1085 85

Angiotensin II receptor blockers represent a class of effective and well tolerated orally active antihypertensive drugs. Activation of AT(1) receptors leads to vasoconstriction, stimulation of the release of catecholamines and antidiuretic hormone and promote growth of vascular and cardiac muscle. AT(1) receptor blockers antagonise all those effects. Losartan was the first drug of this class marketed, shortly followed by valsartan, irbesartan, telmisartan, candesartan, eprosartan and others on current investigation. All these drugs have the common properties of blockading the AT(1) receptor thereby relaxing vascular smooth muscle, increase salt excretion, decrease cellular hypertrophy and induce antihypertensive effect without modifying heart rate or cardiac output. Most of the AT(1) receptor blockers in use controlled blood pressure during the 24 h with a once-daily dose, without evidence of producing tolerance to the antihypertensive effect and being with low incidence of side effects even at long term use. Monotherapy in mild-to-moderate hypertension controls blood pressure in 40 to 50% of these patients; when a low dose of thiazide diuretic is added, 60-70% of patients are controlled. The efficacy is similar to angiotensin-converting enzyme (ACE) inhibitors, diuretics, calcium antagonists and beta-blocking agents. AT(1) receptor blockers are specially indicated in patients with hypertension who are being treated with ACE inhibitors and developed side effects such as, cough or angioedema. The final position in the antihypertensive therapy in this special population and other clinical situations, such as left ventricular hypertrophy, heart failure, diabetes mellitus and renal disease, has to be determined in large prospective clinical trials, some of which are now being conducted and seem promising.
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PMID:Angiotensin II receptor antagonists role in arterial hypertension. 1198 4

The renin-angiotensin-aldosterone system plays a key role in the regulation of fluid and electrolyte balance. Angiotensin-converting enzyme inhibitors inhibit angiotensin-converting enzyme and have been shown to be effective in many cardiovascular diseases. They should be considered for the treatment of hypertension in patients with heart failure, previous myocardial infarction, diabetes, or proteinuria. There are a number of side-effects associated with angiotensin-converting enzyme inhibitors, especially persistent dry cough. Angiotensin II receptor antagonists (sartans) provide a more specific blockade of the renin-angiotensin-aldosterone system and are associated with fewer side-effects, including cough. Their long-term efficacy and tolerability in the treatment of patients with hypertension has, however, yet to be established. Periodic monitoring of renal function and electrolytes is required in patients treated with an angiotensin-converting enzyme inhibitor or a sartan.
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PMID:Blockade of the renin-angiotensin system. 1205 64

The coexistence of diabetes mellitus in hypertensive patients doubles the number of cardiovascular events (relative risk: 1.73-2.77) and cardiovascular mortality (relative risk: 2.25-3.66). Therapeutic interventions concentrating on elevated blood glucose alone for prevention of late complications were not effective in essential reduction of cardiovascular morbidity and mortality. For that reason therapies, focussing on other macrovascular risk factors, did increase significantly in the last decade. Strategies for reduction of the macrovascular risk include the aggressive treatment of hypertension. In the now published hypertension intervention studies in diabetic patients many different objectives were studied. As we already know, lowering of blood pressure does reduce cardiovascular risk. The optimal blood pressure threshold is not known yet, but of major interest. To find the most effective antihypertensive agent and the most effective combination therapy for diabetic patients, the most frequently used antihypertensive agents were compared with each other. Very interesting are the special effects of some substances, which exceed the lowering of blood pressure, like effects on the endothelinn or on coagulation disturbances. These protective and antiatherosclerotic effects could possibly get relevance even in normotensive patients. Concerning this special question, ACE-inhibitors and Angiotensin II receptor antagonists are getting more and more in the focus of interest and seem to be superior compared to other substances. Concluding the existing evidence from hypertension studies the following recommendations can be deduced: Diabetic patients with at least one additional cardiovascular risk factor should get an ACE-inhibitor in combination with other antihypertensive agents or as monotherapy. For combination therapy all the available antihypertensive agents are appropriate and can lower blood pressure adequately.
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PMID:[Reduction of cardiovascular morbidity and mortality by combined antihypertensive drug therapy in patients with type 2 diabetes mellitus]. 1209 90

Diabetes mellitus is the most common cause of end-stage renal disease in the United States, accounting for about 50% of all new cases. Although we previously established the renoprotective benefits of angiotensin converting enzyme (ACE) inhibitors in patients with coexisting hypertension and type 1 diabetes, evidence of the renoprotective effect of ACE inhibitors in patients with type 2 diabetes is less clear. We conducted the Irbesartan Diabetic Nephropathy Trial (IDNT) to determine whether the angiotensin II receptor blocker (ARB) irbesartan slows the progression of nephropathy in patients with type 2 diabetes independently of its blood pressure (BP)-lowering effect. In this randomized, controlled trial, we found that irbesartan was associated with a 20% reduction in the risk for the primary composite end point (doubling of the baseline serum creatinine concentration, development of end-stage renal disease, or death from any cause) compared with placebo (P =.02) and a 23% reduction compared with amlodipine therapy (P =.006). These results were not explained by differences in the BP that was achieved. In a separate study, losartan was shown to reduce the risk for progression of renal disease in patients with type 2 diabetic nephropathy. Angiotensin II receptor blocker therapy has also been demonstrated to slow the progression to overt nephropathy when initiated early in the course of type 2 diabetic renal disease (ie, in patients with microalbuminuria). Based on these studies, ARBs are clearly effective in protecting against the progression of nephropathy due to type 2 diabetes. This protection is independent of their BP-lowering effect. Preclinical studies with the newest ARB, olmesartan medoxomil, suggest that this agent may provide renoprotective benefits as well.
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PMID:The role of angiotensin II receptor blockers in preventing the progression of renal disease in patients with type 2 diabetes. 1238 93

Angiotensin II receptor blockers (ARBs) are effective in controlling blood pressure and have been shown to reduce proteinuria with fewer adverse effects than angiotensin converting enzyme inhibitors. In the present prospective study, we evaluated the action of irbesartan, an ARB with a long half life, on proteinuria, peritoneal protein losses, and peritoneal transport in patients with chronic renal failure (CRF) undergoing peritoneal dialysis (PD). We enrolled 15 stable patients (11 with diuresis of more than 500 mL/day; 40% women; 40% with diabetes) into the study. Mean age of the patients was 65 +/- 15 years, and mean time on PD was 33 +/- 21 months. The study was performed in two stages. In stage I, patients received no irbesartan. In stage II, patients received 30 days of treatment with irbesartan (145 +/- 72 mg/day). After treatment with irbesartan, and no changes in blood pressure level as compared with baseline, we observed a reduction in proteinuria (r = 0.690, p < 0.05), decreased peritoneal protein losses at 4 hours' and 24 hours' dwell time (r = 0.910 and r = 0.930, p < 0.001), decreased peritoneal Kt/V(r = 0.586, p < 0.05), and increased peritoneal creatinine clearance (r = 0.943, p < 0.001). Levels of serum albumin (r = 0.630, p < 0.05), prealbumin (r = 0.810, p < 0.001), and transferrin (r = 0.551, p < 0.05) increased after treatment with irbesartan. We conclude that treatment with irbesartan in patients with CRF undergoing PD modifies peritoneal transport and reduces peritoneal and urinary protein loss. This effect probably has a positive impact on nutritional parameters. Further studies are required to elucidate the mechanisms involved.
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PMID:Effects of angiotensin II receptor blocker (irbesartan) on peritoneal membrane functions. 1538 90

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure emphasizes the urgent need to lower blood pressure (BP) to a goal of <140/90 mm Hg in patients with uncomplicated hypertension and to <130/80 mm Hg in high-risk patients, such as those with diabetes mellitus or chronic kidney disease, to prevent cardiovascular disease morbidity and mortality. Consequently, a meaningful measure of the efficacy of an antihypertensive therapy is its ability to achieve BP reduction to below the recommended BP goals. Angiotensin II receptor blockers (ARB) are highly effective antihypertensive agents with excellent tolerability profiles similar to those of placebo. A literature search using MEDLINE, EMBASE, and BIOSIS to identify studies reporting data on the percentage of patients attaining BP goals found that monotherapy with an ARB can generally result in the attainment of the diastolic BP (DBP) goal of <90 mm Hg in approximately 50% of hypertensive patients. However, to our knowledge, the attainment of the systolic BP (SBP) and combined SBP/DBP goals with ARB monotherapy has not been reported. Therefore, a secondary analysis of BP efficacy data from a published study that directly compared recommended starting doses of four currently marketed ARB was performed to assess combined SBP and DBP goal attainment. This analysis showed that the percentage of patients achieving the combined SBP/DBP goal rate of <140/90 mm Hg was highest with olmesartan medoxomil (32.4%) compared with recommended starting doses of losartan potassium (16.1%), valsartan (14.5%), or irbesartan (25.9%). Optimal ARB monotherapy can achieve recommended BP goals in a significant proportion of hypertensive patients. However, the majority of hypertensive patients will require combination therapy with two or more antihypertensive agents.
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PMID:Role of angiotensin receptor blockers as monotherapy in reaching blood pressure goals. 1575 58

The introduction of Angiotensin II receptor blockers (ARB) in 1995 was another milestone in the pharmacological management of hypertension. Due to the manifold effects on several target organs Angiotensin II is one of the most important mediator in the pathogenesis of hypertension. The blockade of the Angiotensin II receptor type 1 is a crucial cornerstone in interrupting the pathophysiological pathways in hypertension. Furthermore ARB have an excellent tolerability comparable with placebo. In the last decade large placebo-controlled trials could prove the efficiency of ARB in terms of morbidity and mortality. Patients after acute myocardial infarction and patients with chronic heart failure benefit from treatment with ARB equally compared to treatment with ACE inhibitors. Combining ARB and ACE inhibitors in patient after myocardial infarction increases the rate of adverse events without improving survival. Increase of microalbuminuria and worsening of diabetic nephropathy is reduced by ARB in patients with diabetes type 2, but an advantage over ACE inhibitors could not be documented. Hypertensive patients with electrocardiographically left ventricular hypertrophy treated with ARB seem to have an additional benefit in terms of morbidity and mortality compared to treatment with beta-blockers. In the early treatment of stroke patients treated with ARB have a lower 12-mounth mortality than patients receiving placebo. In conclusion, Angiotensin II receptor blockers are due to their well proved efficiency, the cardio- and renoprotective qualities and the excellent tolerability profile a useful therapeutic option in the management of patients with hypertension.
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PMID:[Angiotensin II receptor blockers--evidence along the cardiovascular continuum]. 1588 24

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