Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiogenesis, cellular growth and invasion of a cancer cell are attractive targets for new treatment strategies of malignancies in recent years. The evidences are accumulating that ACE inhibitors and angiotensin II type 1 antagonists could be novel anti-angiogenic, anti-invasive, and even anti-growth agents against neoplastic tissues: The renin-angiotensin system promotes angiogenesis directly or indirectly and growth of neoplastic cell. Some tumors carry angiotensin II type 1 receptors. Angiotensin II antagonists and angiotensin-I-converting enzyme inhibitors have shown some anti-neoplastic actions. Angiotensin II receptor blocker losartan antagonises platelets, which are thought to modulate via vascular endothelial growth factor. They may even protect the patient from the major toxicity of chemotherapy and/or radiotherapy, myelotoxicity, enabling us to give higher doses and end up with higher success rate. We believe that these agents can be useful on clinical grounds and suggest their incorporation into clinical studies.
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PMID:Old antihypertensives as novel antineoplastics: angiotensin-I-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists. 1220 67

Angiotensin II receptor blockers (ARBs) directly inhibit the angiotensin II type 1 receptors, which suppresses the renin-angiotensin-aldosterone system (RAAS). Six ARBs are approved in Canada for the treatment of hypertension, none are yet approved for the treatment of heart failure (HF). Evidence comparing ARBs to angiotensin converting enzyme inhibitors (ACEIs) in HF is still limited. A recent meta-analysis of 17 clinical trials could not confirm that ARBs are superior to ACEIs in reducing either mortality or hospitalization in HF patients. ARBs may be used as an alternative in HF patients intolerant of ACEIs. A meta-analysis indicates that, compared to using an ACEI alone, adding an ARB to an ACEI carries the potential for additional benefits in terms of reduced hospitalization, but not mortality. However, the FDA determined there is currently insufficient evidence of such additional benefit when valsartan is combined to an ACEI in patients with HF.
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PMID:Heart failure: is there a role for angiotensin II receptor blockers? 1224 2

Recently, both researchers and clinicians have focused their attention to the blockade of the renin-angiotensin system (RAS). Their efforts resulted in discovery of ACE inhibitors. ACE inhibitors proved to be effective antihypertensive drugs. However, their excellent antihypertensive efficacy has been limited by frequent occurrence of adverse effects, among which cough occupies a prominent place. Angiotensin II receptor antagonists could completely block RAS, having significantly less adverse effects than ACE inhibitors. Clinical studies have demonstrated that angiotensin II receptor antagonists are equally effective in the treatment of hypertension as diuretics, beta blockers, calcium antagonists and ACE inhibitors. Also the studies showed angiotensin II receptor antagonists to have an additional advantage, i.e. the frequency of their adverse effects matches that of placebo. All today available angiotensin II receptor antagonists--losartan, valsartan, irbesartan, candesartan, eprosartan, and telmisartan--equally lower both systolic and diastolic pressure. This new class of drugs can be used as monotherapy or can be combined with other antihypertensive drugs, especially with diuretics. Trials now underway will demonstrate whether angiotensin II receptor antagonists can prevent target-organ damage and reduce cardiovascular morbidity and mortality.
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PMID:[Role of angiotensin II antagonists in the treatment of hypertension]. 1237 64

The continued poor rates of blood pressure (BP) control to the recommended target BP of <140/90 mm Hg in patients with hypertension indicate a persistent need for improved antihypertensive therapy. Angiotensin II receptor blockers (ARBs) constitute the newest approved class of antihypertensive agents. As with angiotensin converting enzyme inhibitors, ARBs block the renin-angiotensin-aldosterone system, but do so through a more specific mechanism. Angiotensin converting enzyme inhibitors block the conversion of angiotensin I to angiotensin II, but angiotensin II may be produced by several alternate pathways. Angiotensin II receptor blockers, by contrast, inhibit the binding of angiotensin II to the angiotensin II type 1 (AT1) receptor, independent of the pathway of angiotensin II production. Comparative safety and efficacy trials indicate that ARBs are similar to other antihypertensive drugs in terms of BP-lowering effectiveness and have superior tolerability. Olmesartan medoxomil is the newest and one of the most effective of the ARBs. In controlled trials, it has been shown to provide 24-h BP control with antihypertensive efficacy at least as good as that of the calcium channel blockers amlodipine besylate and felodipine and the beta-blocker atenolol. In a comparative study, olmesartan medoxomil demonstrated significantly greater reductions in diastolic BP than did three other leading ARBs-losartan potassium, irbesartan, and valsartan. With the convenience of placebo-like tolerability and once-daily dosing, combined with excellent antihypertensive efficacy, olmesartan medoxomil may be a useful addition to our management of hypertension.
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PMID:Strategies to meet lower blood pressure goals with a new standard in angiotensin II receptor blockade. 1238 91

Percutaneous transluminal coronary angioplasty (PTCA) and stent implantation are useful techniques for treating patients with coronary atherosclerosis. However, the long-term efficacy of these treatment is limited by vascular restenosis, which occurs after these procedures. Although ACE inhibitor cilazapril prevented the neointimal hyperplasia of rat carotid artery after balloon injury, it did not lead to prevention of restenosis after PTCA in human studies (MERCATOR and MARCATOR). Angiotensin II receptor blocker, candesartan, inhibited the neointimal formation after balloon injury in both rat and dog. Val-PREST trial showed that valsartan reduced the in-stent restenosis rate after stent implantation. The inhibition of renin-angiotensin system by angiotensin II receptor blocker may help to prevent restenosis after angioplasty.
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PMID:[Preventing effect of angiotensin II receptor blocker on neointimal hyperplasia after vascular injury]. 1239 91

Angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors have been shown to reduce morbidity and mortality in patients with heart failure, but their inhibitory actions on angiotensin I-induced increases in blood pressure in heart failure are not clear. Angiotensin I blocking and cardioprotective properties of the angiotensin II receptor blocker candesartan and the angiotensin-converting enzyme inhibitor quinapril were studied in a rat model of dilated cardiomyopathy after autoimmune myocarditis. Low-dose candesartan (0.5 mg/kg) showed the same angiotensin I blocking action as high-dose quinapril (20 mg/kg) in rats with heart failure. Twenty-eight days after immunization, surviving Lewis rats (43/58, 74%) were divided into three groups and given quinapril at 20 mg/kg per day (group Q, n = 14), candesartan at 0.5 mg/kg per day (group C, n = 14) or vehicle alone (group V, n = 15). After oral administration for 1 month, four of 15 (27%) rats in group V and two of 14 (14%) in group C died. None of the animals in group Q died. Although angiotensin II levels of the blood and the left ventricle in group V [367 +/- 26 and 437 +/- 18% versus normal rats (group N)] were significantly higher than those in group N (both p < 0.01), they were reduced in group Q (88 +/- 32 and 169 +/- 53%, both p < 0.01). The left ventricular end-diastolic pressure and the area of myocardial fibrosis were lower, and the first derivative +/-dP/dt was higher in group Q (7.0 +/- 1.7 mmHg, 9 +/- 3% and +3451+/- 170/-3182 +/- 186 mmHg/s, respectively) than in group V (16.7 +/- 1.3 mmHg, 36 +/- 6% and +2601 +/- 235/-2156 +/- 257 mmHg/s, respectively) and in group C (11.2 +/- 2.0 mmHg, 26 +/- 4% and +3063 +/- 164/-2734 +/- 174 mmHg/s, respectively). Although levels of expression of transforming growth factor beta1 and collagen III mRNA in groupV (367 +/- 26 and 437 +/- 18% versus group N) were significantly higher than those in group N (both p < 0.01), they were reduced in group Q (88 +/- 32 and 169 +/- 53%, both p < 0.01). These results suggested that although low-dose candesartan can block increases in blood pressure with circulating angiotensin I to the same extent as high-dose quinapril, it does not confer sufficient protection against injury from the renin-angiotensin system in heart failure.
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PMID:Comparative effects of angiotensin II receptor blockade (candesartan) with angiotensin-converting enzyme inhibitor (quinapril) in rats with dilated cardiomyopathy. 1269 79

The blockade of the renin-angiotensin system in the heart failure using ACE inhibitors, based on numerous clinical studies, demonstrated significant decrease in morbidity and mortality in the patients. Discovery of angiotensin II receptor antagonists brought about a new possibility of blockade of the rennin-angiotensin system. The blockade of the renin-angiotensin system with angiotensin II receptor antagonists should have been more effective and comprehensive than that induced by ACE inhibitors. However, the first studies with angiotensin II receptor antagonists in heart failure did not confirm that the antagonists are superior in reducing mortality and hospitalization in patients with heart failure when compared with ACE inhibitors. For the time being, the ACE inhibitors remain the current therapy of choice in treating heart failure. Angiotensin II receptor antagonists are a reasonable alternative in patients who cannot be treated with ACE inhibitors because of adverse effects. Clinical studies currently under way with angiotensin II receptor antagonists may alter these conclusions.
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PMID:[Angiotensin II antagonists in the treatment of cardiac decompensation]. 1282 85

A growing body of evidence indicates that the renin-angiotensin system and insulin resistance play crucial roles in left ventricular hypertrophy (LVH) in patients with essential hypertension (EH). Angiotensin II receptor blockers (ARB) have been reported to regress LVH and improve insulin resistance. We tested the hypothesis that candesartan, an ARB, could regress LVH, in association with improvement of insulin resistance in EH patients. The study participants were nondiabetic and never-treated EH patients (n = 10). Candesartan was administered at a mean final dose of 10.4 +/- 2.1 mg/d for 24 weeks. Candesartan treatment resulted in a significant decrease of systolic and diastolic blood pressures, LV mass index (LVMI), homeostasis model assessment (HOMA) index, and plasma brain natriuretic peptide (BNP). A significant correlation was observed between the percent decrease in LVMI and that of both the HOMA index (r = 0.83, P <.001) and BNP (r = 0.71, P <.005). Stepwise regression analyses revealed that the percent decrease of HOMA index was an independent predictor for both percent decrease in LVMI and plasma BNP. Our findings suggest that pharmacological blockade of angiotensin II receptors by candesartan could improve LVH in never-treated EH patients, which may relate to the improvement of insulin resistance.
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PMID:Candesartan, an angiotensin II receptor blocker, improves left ventricular hypertrophy and insulin resistance. 1516 28

Blood pressure, together with proteinuria, represents one of the most important factors in the progression of chronic renal failure (CRF). Antihypertensive therapy is beneficial to slow down the progression of a variety of chronic renal diseases, no matter what the cause. Intraglomerular hypertension, increased glomerular permeability and proteinuria should be identified, since they can be treated to prevent or minimize further glomerular injury. But not all antihypertensive drugs are equally effective to prevent the progression of CRF. Recent large trials indicate that blood pressure lowering obtained by intervention in the renin-angiotensin-aldosterone system (RAAS) has an additive renoprotective effect in diabetic and nondiabetic renal diseases. In nondiabetic patients, the AIPRI and REIN studies support that angiotensin-converting enzyme (ACE) inhibitors have a long-term renoprotective effect. The benefits of ACE inhibitors can be demonstrated even in patients who are not hypertensive. Angiotensin II receptor antagonists are shown to be renoprotective in type 2 diabetics (RENAAL and IDNT). However, whether these renoprotective effects are due to blood pressure reduction or due to the specific pharmacologic RAAS blockade is still a matter of debate. This discussion is still open, because the reduction in blood pressure levels was lower in patients treated with a drug that interferes with the RAAS compared with other antihypertensive regimens. It is concluded that both ACE inhibitors and AT II receptor antagonists are lowering the intraglomerular pressure independent of any change in systemic blood pressure by dilatation of the efferent arteriole of the glomerulus. These additional nonpressure-related effects may protect renal function by their antiproteinuric effect. In addition, beneficial effect of ACE inhibitors are related to reduction of AT II, which has potent proinflammatory effects independent of its hemodynamic influences. Other drugs, such as diuretics, beta blockers, and hydralazine, do not induce efferent dilatation and, therefore, may be less likely to reverse intraglomerular hypertension. For example, hydralazine and nifedipine appear to produce prominent afferent or preglomerular arteriolar dilatation. This will allow more of the systemic pressure to be transmitted to the glomerulus. Therefore, short-acting dihydropyridine calcium channel blockers (CCB) are not recommended. By comparison, long-acting dihydropyridines such as diltiazem and verapamil are less potent vasodilators and may primarily decrease the resistance of the efferent arteriole, similar to the ACE inhibitors. They may have an antiproteinuric activity. Yet, there is lack of large prospective randomized trials.A beta blocker as antihypertensive agent is indicated as second- or third-line drug especially in patients with additional cardiovascular disease. Other antihypertensive drugs can be added as necessary to achieve the treatment goals for arterial hypertension. The use of a diuretic will often be helpful in patients who already have renal insufficiency, since fluid overload is an important cause of hypertension and may also enhance the effectiveness of drugs that interfere with the RAAS. alpha(1)-receptor or sympathetic blockers are further possible drugs for combination antihypertensive therapy.
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PMID:[Are all antihypertensive drugs renoprotective?]. 1516 50

Almost 5 million individuals in the United States are diagnosed with chronic heart failure (HF), and the prevalence is increasing. Angiotensin-converting enzyme (ACE) inhibitors and beta blockers, neurohormonal antagonists that block the renin-angiotensin system (RAS) and the sympathetic nervous system, respectively, have been shown in clinical trials to reduce morbidity and mortality in patients with HF, and these therapies are now integral components of standard HF treatment. Yet, morbidity and mortality rates in HF remain unacceptably high, and the limitations of current standard therapies are becoming increasingly apparent. About 10% of patients with HF are unable to tolerate ACE inhibitors, often because of cough. In addition, ACE inhibition may not completely block the RAS because angiotensin II, the main end product of the RAS, can be generated via non-ACE enzymatic pathways. Angiotensin II receptor blockers (ARBs) may exert more complete RAS blockade than ACE inhibitors by interfering with the binding of angiotensin II at the receptor level, regardless of the enzymatic pathway of production. They are also better tolerated than ACE inhibitors and have been shown to improve symptoms and function in clinical trials in patients with HF. These factors provide a strong rationale for the study of the clinical effects of ARBs in patients with HF.
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PMID:Rationale for the use of angiotensin II receptor blockers in patients with left ventricular dysfunction (part I of II). 1597 54


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