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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The renin-angiotensin system is a key target for drugs combating cardiovascular disease. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor type-1 (AT1 receptor) blockers are well known. However, angiotensin peptides can be generated through a number of pathways besides the classic system. This review outlines some of these pathways, their relation to the classic system and the likely effect of inhibiting them. Renin is still the key enzyme in angiotensin peptide generation and seems to be the only route to angiotensin I formation in vivo. Renin inhibitors may have some advantages in terms of specificity. Also, by blocking angiotensin I generation, the production of downstream bioactive angiotensin I metabolites should also be blocked. Chymase, a mast cell serine protease, cleaves angiotensin I to produce angiotensin II and may be important at sites of inflammation such as atherosclerotic plaque. Angiotensin-converting enzyme 2 (ACE2), a carboxypeptidase structurally related to ACE but resistant to ACE inhibitors, has a protective effect on cardiac function. Neutral endopeptidase 24.11 breaks down both atrial natriuretic peptide and angiotensin II. Inhibiting it potentiates the action of endogenous atrial peptide but only affects circulating angiotensin II when basal levels are above normal. Dual inhibitors of ACE and endopeptidase 24.11 may be of value where there is both sodium retention and increased angiotensin II. Targeting the renin-angiotensin system by gene therapy or antibody treatment may provide a longer-term treatment for hypertension.
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PMID:Targeting the renin-angiotensin system: what's new? 1563 41

Renin-angiotensin (Ang) system (RAS) peptides injected into the periaqueductal gray matter (PAG) elicit antinociception. Saralasin blocks Ang II-elicited antinociception. Thus, it is possible that endogenous RAS peptides could participate on the modulation of nociception in the PAG. This possibility was tested here injecting, in the PAG, the specific Ang type 1 and type 2 receptor (AT1 receptor and AT(2 receptor) antagonists losartan and CGP42,112A, respectively, either alone or before Ang II. The effects of Ang II, losartan and CGP42,112A on nociception were measured using the tail flick test and the model of incision allodynia. Ang II increased tail-flick latency, an effect inhibited by both losartan and CGP42,112A. Ang II reduced incisional allodynia. Either losartan or CGP42,112A alone increased incision allodynia, suggesting that endogenous Ang II and/or an Ang-peptide participates in the control of allodynia by the PAG. AT1 and AT2 receptors were immunolocalized in neuronal cell bodies and processes in the ventrolateral PAG. Taken together, the antinociceptive effect of Ang II injection into the ventrolateral PAG, the increase of allodynia elicited by injecting either losartan or CGP42,112A alone in the PAG, and the presence of AT1 and AT2 receptors in neurons and neuronal processes in the same region, represent the first evidence that part of the tonic nociceptive control mediated by the PAG is carried out locally by endogenous Ang II and/or an Ang-peptide acting on AT1 and AT2 receptors.
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PMID:A new role for the renin-angiotensin system in the rat periaqueductal gray matter: angiotensin receptor-mediated modulation of nociception. 1580 96

The renin-angiotensin system is implicated in the pathophysiology of hypertension. Renin release is regulated by a number of factors, including circulating Ang II (angiotensin II), the so-called short feedback loop. The aim of the present study was to investigate the responsiveness of circulating Ang II on PRA (plasma renin activity) in normotensive subjects with a PFH or NFH (positive or negative family history of hypertension respectively). PRA, renal haemodynamics and urinary sodium excretion were measured during infusion of Ang II without and with pretreatment with the AT1 (Ang II type 1) receptor blocker irbesartan. Normotensive men with a PFH (n=13) and NFH (n=10), with a mean age of 38 years, were given on different occasions intravenous Ang II infusions of 0.1, 0.5 and 1.0 ng.kg-1 of body weight.min-1 before and after pretreatment with 150 mg of irbesartan once a day for 5 consecutive days. RPF (renal plasma flow) and GFR (glomerular filtration rate) were also measured. Before Ang II infusion, the PFH and NFH groups did not differ with respect to BP (blood pressure), body mass index, PRA, RBF (renal blood flow) or urinary sodium. There was no difference in BP or renal haemodynamic response to the highest Ang II dose between the groups. PRA declined with the highest Ang II dose (P<0.01) in subjects with a NFH, but not in subjects with a PFH. After treatment with irbesartan when Ang II had no effect on BP in either group, Ang II also suppressed PRA in subjects with a PFH (P<0.01), and the difference between the groups at baseline was thus eliminated. In conclusion, these findings indicate that subjects with a PFH have a defective Ang II suppression of PRA, which is corrected by AT1 receptor blockade.
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PMID:Failure of angiotensin II to suppress plasma renin activity in normotensive subjects with a positive family history of hypertension. 1590 Dec 42

Targeting the renin-angiotensin-aldosterone system (RAAS), specifically the effector peptide angiotensin II (Ang II), represents a major opportunity for slowing the progression of cardiovascular disease (CVD) and, in turn, reducing the risk of morbidity and mortality. Inhibition of angiotensin-converting enzyme (ACE) and selective blockade of Ang II AT1 receptors are two approaches through which the pathophysiological effects of Ang II can be targeted. Numerous clinical studies have established the benefits of ACE inhibitors (ACE-Is) in lessening the morbidity and mortality burden of CVD. There are, however, tolerability concerns associated with ACE-Is, such as angioedema and dry cough. By blocking Ang II at the AT1 receptor level, Ang II receptor blockers (ARBs) provide a more specific and complete blockade of the deleterious effects of Ang II and tend to have more favourable tolerability. A number of clinical trials have shown that ARBs are not only associated with positive outcomes across the CVD continuum but mat also have a role in the prevention or delay of diabetes (a major cardiovascular risk factor). Ongoing trials are aiming to define the place of such agents in lessening morbidity and mortality from CVD.
J Renin Angiotensin Aldosterone Syst 2006 Jun
PMID:Clinical evidence for the cardiovascular benefits of angiotensin receptor blockers. 1696 48

Although in the developed world the incidence of and mortality from coronary heart disease (CHD) and stroke have been declining over the last 15 years, heart failure is increasing in incidence, prevalence and overall mortality, despite advances in the diagnosis and management of the condition. Hypertension, alone or in combination with CHD, precedes the development of heart failure in the majority of both men and women. Whilst there have been improvements in the overall management of hypertension, as reflected in rates of diagnosis, awareness, treatment and control of blood pressure (BP), there are still many patients with hypertension who remain undiagnosed or untreated and of those who do receive treatment many fail to achieve current targets for BP control. Placebo-controlled trials in hypertension, largely based on diuretic and beta-blocker-based regimens, have unequivocally demonstrated that the treatment of hypertension can significantly reduce the incidence of heart failure. Newer treatment strategies offer theoretical and proven practical advantages over established antihypertensive therapy. In particular, AT1-receptor blockers appear to provide benefits beyond BP control and are effective in the treatment of both hypertension and heart failure. Thus, the primary prevention of heart failure in hypertensive patients should be based upon strategies that provide tight and sustained BP control necessitating the use of multiple drugs. However, there is now compelling evidence to suggest that this therapy should include an antihypertensive agent that inhibits the reninangiotensin- aldosterone system (RAAS).
J Renin Angiotensin Aldosterone Syst 2006 Jun
PMID:From hypertension to heart failure -- are there better primary prevention strategies? 1708 60

Angiotensin-converting enzyme (ACE) inhibitors may reduce urinary albumin excretion (UAE) by decreasing glomerular pressure and increasing glomerular charge selectivity through preservation of glycosaminoglycans. The effect of Angiotensin II antagonism on glomerular charge selectivity remains to be determined. The aim of this study was to compare the effects of an AT1 blocker losartan and an ACE inhibitor (ACE-I) enalapril on UAE, extracellular matrix proteins, glycosaminoglycan excretion (UGAG) and red blood cell anionic charge (RBCCh) which are the indirect markers of glomerular basement membrane anionic content in hypertensive Type 2 diabetic patients. Twenty-four patients were randomised into two groups and received either enalapril (520 mg/d) or losartan (50100 mg/d). All parameters were measured at baseline and after six months of treatment. At the end of six months, systolic and diastolic blood pressures (BP), UAE rates, UGAG excretion and RBCCh were significantly and equally reduced in both treatment groups compared with baseline. RBCCh was negatively correlated with UAE (r=-0.57, p<0.0001) and UGAG excretion (r=-0.57, p<0.0001); UAE was correlated with UGAG excretion (r=0.58, p<0.0001). In conclusion, enalapril and losartan treatment were equally effective in reducing BP, UAE as well as UGAG excretion and preserving RBCCh in hypertensive Type 2 diabetic patients. ACE inhibition and AT1-receptor blockade may have favourable effects on preserving glomerular anionic content in hypertensive diabetic patients.
J Renin Angiotensin Aldosterone Syst 2006 Jun
PMID:Effects of ACE inhibition and angiotensin II receptor blockade on glomerular basement membrane protein excretion and charge selectivity in type 2 diabetic patients. 1708 64

Angiotensin II (Ang II) plays a key role in the regulation of blood pressure and fluid homeostasis. Valsartan is a highly selective Ang II receptor blocker that specifically and selectively blocks Ang II at the AT1-receptor. In animal models, valsartan has shown positive effects on vasoconstriction, proliferation, remodelling, endothelial function and thrombogenesis, inflammation and atherosclerosis. These data are likely to be confirmed by the results of current clinical trials and valsartan is set to provide improved cardiovascular therapy in the future.
J Renin Angiotensin Aldosterone Syst 2000 Jun
PMID:New basic science initiatives with the angiotensin II receptor blocker valsartan. 1719 10

The advent of specific angiotensin II (Ang II) receptor blockers (ARBs) some ten years ago has provided substantial information on the specific actions of the AT1- and AT2-receptors. Most of the early research concentrated on the AT1-receptor, and the actions and biological roles of the AT2-receptor are much less well characterised. The AT2-receptor is involved in the inhibition of cell proliferation, and in cell differentiation and development, regeneration and apoptosis. By raising local Ang II concentrations at the AT2-receptor, selective blocking of the AT1-receptor may therefore have beneficial effects. This concept may be important for antihypertensive therapy and in cardiovascular disease in general.
J Renin Angiotensin Aldosterone Syst 2000 Jun
PMID:Angiotensin receptor blocker selectivity at the AT1- and AT2-receptors: conceptual and clinical effects. 1719 11

Patients treated for hypertension are still at significantly elevated risk for cardiovascular complications when compared with normotensive patients, even when on antihypertensive therapy. In all fairness though, a majority of these patients have uncontrolled blood pressure. Blocking the renin-angiotensin-aldosterone system (RAAS) prevents or reverses cardiac remodelling and improves prognosis in cardiovascular disease beyond the effects on blood pressure (BP). Valsartan acts by selectively blocking the AT1-receptor and shows similar efficacy and improved tolerability compared with ACE inhibitors. This drug may provide additional benefits in controlling the cardiovascular complications of hypertension. Results of large clinical trials with valsartan, such as VALUE, Val-HEFT, VALIANT and ABCD-2V, are eagerly awaited.
J Renin Angiotensin Aldosterone Syst 2000 Jun
PMID:Valsartan and the renin-angiotensin-aldosterone system: blood pressure control and beyond. 1719 13

Angiotensin-converting enzyme (ACE) inhibitors have a well-established role in the management of patients with hypertension, diabetes, heart failure and myocardial infarction (MI). ACE inhibitors have been particularly well studied in acute and chronic MI with consistent and substantial survival benefits demonstrated, particularly in the higher risk groups. The recent development of angiotensin II (Ang II) receptor blockers (ARBs) as a well tolerated pharmacological therapy to more completely inhibit the actions of Ang II at the AT1-receptor level raises questions concerning comparative efficacy with the proven ACE inhibitor experience. Two major trials will provide a direct comparison of ARBs with an ACE inhibitor. The Valsartan in Acute Myocardial Infarction (VALIANT) trial is specifically designed to compare and contrast the ARB, valsartan, used both alone as well as in combination with a proven ACE inhibitor regimen, in a high risk MI population. VALIANT, with its three arms targetting 14,500 patients, is uniquely poised to determine whether the pharmacological advance in the development of ARBs confers additional clinical (survival) value in high risk MI patients.
J Renin Angiotensin Aldosterone Syst 2000 Jun
PMID:Will more complete inhibition of the RAAS with angiotensin receptor blockade improve survival following myocardial infarction? 1719 21


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