Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The arrival of angiotensin converting enzyme inhibitors (ACE), and AT1 angiotensin selective receptors blockers, has changed the panorama of systemic high blood pressure and cardiac insufficiency treatments. These inhibitors and blockers have also been useful in cases of left asymptomatic ventricular dysfunction, myocardial infarction and post-infarction and various nephropathies--not only diabetes dependent but due to other etiologies as well. Furthermore, its application in primary prevention of coronary cardiopathies has started to become evident. The main advantages of this new group of drugs are their relative harmlessness and lesser undesirable side effects, as those caused by other antihypertensives agents. The AT1 receptor inhibitors of angiotensin have actually not proven to be superior than the ACE inhibitors (although the latter are not worse) but are better tolerated and protect a greater period of time with a single dosage. A greater number of macro studies with selective AT1 receptor blockers is necessary to know its right place in therapeutics.
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PMID:[Converting enzyme inhibitors or AT1 receptor blockers]. 1156 29

Activation of the RAAS has been linked with an increased risk of myocardial infarction and stroke,(1,2,37,38) and recently these beneficial effects have, in part, been attributed to the effects of the RAAS on the fibrinolytic system. Indeed, ACE seems to occupy a central position in modulating the fibrinolytic balance, where an angiotensin II-mediated increase of PAI-1 plays a major role. By contrast, the effect on bradykinin stimulated t-PA release may be of lesser importance, although the data are conflicting. Importantly, the impact of the RAAS on the fibrinolytic balance may also contribute to the favourable effects of ACE inhibition and AT1-receptor antagonists on cardiovascular events, particularly when considering the activation of the RAAS in hypertension and heart failure. More work is clearly required in this area to elucidate potential therapeutic targets.
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PMID:The renin-angiotensin-aldosterone system and fibrinolysis. 1188 Oct 31

We investigated the haemodynamic parameters and the regulation of cardiac mRNA levels of the angiotensin receptor subtypes, AT1 and AT2, by the AT,-receptor antagonist losartan in rat heart during the acute phase of myocardial infarction. AT1- andAT2-receptor mRNA levels markedly increased at 30 minutes and peaked at 24 hours post myocardial infarction (12.6-fold increase for AT1- and 17.2-fold increase for AT2 compared with controls). Losartan significantly reduced mean blood pressure in sham-operated rats and decreased mean blood pressure and left ventricular end-diastolic pressure in myocardial infarction rats. However, the AT,- andAT2-receptor mRNA levels of losartan-treated rats showed a pattern similar to that of water-treated rats. The time-dependent increase of AT1- and AT2-receptor mRNA levels is associated with the early remodelling process of non-infarcted myocardium post MI and is independent of AT1-receptor blockade.
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PMID:Effects of losartan on haemodynamic parameters and angiotensin receptor mRNA levels in rat heart after myocardial infarction. 1188 Oct 34

Captopril, the classic inhibitor of the angiotensin converting enzyme, was employed in several large clinical studies in recent years. The effect of captopril was compared either with placebo, or captopril was selected as the reference ACE inhibitor for comparison with another therapy. In the classic study SAVE, captopril administered to patients after myocardial infarction with a dysfunction of the left chamber reduced mortality by 19%. Though in the study ELITE the AT1 blocker losartan was more effective to reduce mortality in patients with chronic heart failure than captopril, the larger and mortality-oriented study ELITE II did not demonstrate a difference in mortality reduction between captopril and losartan. ACE inhibitors thus remain drugs of choice in chronic heart failure. AT1 blockers are to be used in the cases when ACE inhibitors are not tolerated. The study CAPPP has demonstrated that captopril in hypertonic patients not only effectively decreases blood pressure but exerts a similar effect on mortality reduction as the classic treatment with a diuretic and a betablocker, the most effective being captopril in diabetic patients. Administration of captopril in hypertonic patients with diabetes mellitus in the study UKPDS had an effect on mortality reduction as well as micro- and macrovascular complications of diabetes similar to that of atenolol. The ongoing study VALIANT compares the AT1 blocker valsartan or a combination of valsartan and captopril with captopril alone on patients at risk after myocardial infarction. Also at the beginning of the 21st century captopril maintains a stable position in the treatment of the cardiovascular system.
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PMID:[The ACE inhibitor, captopril, in the light of new clinical studies]. 1192 78

Scientific evidence currently available supports the concept that renin-angiotensin blockade with angiotensin converting enzyme inhibitors as a first-line treatment exhibits in arterial hypertension beneficial effects in the prevention of mortality and morbidity comparable to those achieved with diuretics and beta-blockers. In addition, the renin-angiotensin blockade has also proved to be beneficial in the secondary prevention of several complications of hypertensive disease such as after myocardial infarction and congestive heart failure, as well as in the prevention of the incidence of type 2 diabetes, and the progression of diabetic and nondiabetic nephropathy. In this later regard, recent evidence with angiotensin II receptor antagonists in reducing the progression of nephropathy in type 2 diabetes strongly confirms that antagonism of the renin-angiotensin system is an effective approach to cardiovascular and renal disease. Finally, the renin-angiotensin blockade in high-risk patients may reduce cardiovascular mortality independently of the effect on blood pressure (BP). The effect of other antihypertensive drugs on cardiovascular risk in patients with high-normal BP should be investigated to establish whether they exhibit a comparable effect or whether there is a class-related benefit of drugs blocking the renin-angiotensin system. Such a strategy could also be encouraged to design future interventional studies with the newer classes of compounds (angiotensin II AT1-receptor antagonists, vasopeptidase inhibitors, endothelin antagonists), which would have the additional potential advantage of providing information more easily transferable to large-scale clinical practice.
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PMID:ACE inhibition and cardiovascular mortality and morbidity in essential hypertension: the end of the search or a need for further investigations? 1199 Dec 25

The LIFE study ("Losartan Intervention For Endpoint reduction in hypertension study") demonstrated a significant cardiovascular protection by an angiotensin AT1 receptor antagonist, losartan, in hypertensive patients with left ventricular hypertrophy. At similar blood pressure control, losartan, as compared to atenolol, reduced the relative risk of primary cardiovascular event (death, myocardial infarction, or stroke) by 13% (p = 0.021) in the whole cohort of 9.193 patients after a mean follow-up of 4.7 years. In a subgroup of 1.195 diabetic patients, the protection was even more marked with a reduction of the combined risk of 24% (p = 0.031) and a fall of the mortality of 39% (p = 0.002). In conclusion, losartan prevents cardiovascular morbidity and death more effectively than atenolol, and seems to confer benefits beyond reduction in blood pressure.
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PMID:[Clinical study of the month. The LIFE study: cardiovascular protection of hypertensive patients by losartan]. 1207 99

ACE-inhibitors and AT, receptor antagonists play an important role in the treatment of cardiovascular and renal diseases. The criteria of evidence-based medicine indicate that ACE-inhibitors (in appropriate combinations with other cardiovascular agents) continue to represent the treatment of first choice in chronic heart failure, post-myocardial infarction with compromised ventricular function, high cardiovascular risk, and diabetic (type 1) nephropathy. It is here that the AT1 antagonists should be used--in particular when ACE-inhibitors are not tolerated. The AT1 antagonists, Irbesartan and Losartan, are applied, at appropriately high doses, primarily in hypertensives with diabetic (type 2) nephropathy. With the current exception of chronic heart failure, no confirmed data are yet available on the value of combination treatment. The LIFE study has shown that an AT1 antagonist is superior to an established beta blocker in hypertensives with an increased risk (left-ventricular hypertrophy), in particular when diabetes mellitus is impending or already present.
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PMID:[ACE inhibitor or AT1 antagonist. Is there a differential therapy?]. 1213 23

ACE inhibition protects the heart against ischemic injury by reducing angiotensin II and promoting bradykinin (BK) accumulation. Since neutral endopeptidase (NEP) metabolizes BK, we determined its activity after induction of myocardial infarction (MI) and examined whether it is influenced by treatment with an ACE inhibitor or AT1 receptor blocker. Rats were studied 6 days and 3 wk after coronary occlusion. Starting 48 h after MI induction, additional animals were treated with the ACE inhibitor quinapril (2 mg x kg(-1) x day-1) or the AT1 blocker irbesartan (50 mg x kg(-1) x day-1). Animals were hemodynamically characterized. Finally, NEP-specific activity and BK concentrations were detected in homogenates of heart compartments. Quinapril and irbesartan treatment improved left ventricular function 6 days and 3 wk after MI induction, and NEP activity was elevated only in the infarcted area of untreated compared with sham-operated rats. After 6 days, irbesartan reversed this increase by 80% and quinapril by 35%. Quinapril had no effect after 3 wk, whereas irbesartan almost completely blocked the increased NEP activity in the infarcted area and concomitantly induced a further rise in the BK concentrations. These results indicate mechanisms of NEP regulation influenced by the AT1 receptor. Our data suggest that NEP is more decisive than ACE in mediating BK degradation and may indicate BK involvement in the cardioprotective effects of AT1 antagonists.
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PMID:AT1 receptor blockade increases cardiac bradykinin via neutral endopeptidase after induction of myocardial infarction in rats. 1215 91

Angiotensin II (Ang II) acts mainly on two receptor subtypes: AT1 and AT2. Most of the known biological actions of Ang II are mediated by AT1 receptors; however, the role of AT2 receptors remains unclear. We tested the hypothesis that the cardioprotective effects of AT1 receptor antagonists (AT1-ant) after myocardial infarction (MI) are partially mediated by activation of AT2 receptors; thus in AT2 receptor gene knockout mice (AT2-/Y), the effect of AT1-ant will be diminished or absent. MI was induced by ligating the left anterior descending coronary artery. Four weeks later, AT2-/Y and their wild-type littermates (AT2+/Y) were started on vehicle, AT1-ant (valsartan, 50 mg/kg per day), or ACE inhibitor (enalapril, 20 mg/kg per day) for 20 weeks. Basal blood pressure and cardiac function as well as remodeling after MI did not differ between AT2+/Y and AT2-/Y. AT1-ant increased ejection fraction and cardiac output and decreased left ventricular diastolic dimension, myocyte cross-sectional area, and interstitial collagen deposition in AT2+/Y, and these effects were significantly diminished in AT2-/Y. ACE inhibitors improved cardiac function and remodeling similarly in both strains. We concluded that (1) activation of AT2 during AT1 blockade plays an important role in the therapeutic effect of AT1-ant and (2) the AT2 receptor may not play an important role in regulation of cardiac function, either under basal conditions after MI remodeling or in the therapeutic effect of ACE inhibitors.
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PMID:Role of AT2 receptors in the cardioprotective effect of AT1 antagonists in mice. 1221 61

Because it is uncertain whether high-pressure stent deployment may contribute to more exuberant neointimal proliferation, a new stent, the LP , was constructed to allow full expansion at 10 atmospheres (atm). We compared in a randomized trial the 6-month target vessel revascularization (TVR) and other clinical outcomes of the LP stent with the most commonly used Food and Drug Administration-approved stent (Guidant Duett and Tristar stents) in 1,003 patients without a recent myocardial infarction. The first 150 patients assigned the LP stent also underwent repeat angiography at 6 months. Baseline characteristics for the two groups were balanced, except for an excess of unstable angina in the LP group. There was slight excess in failure to deliver the LP stent (3.4% versus 1.4%; p = 0.04), and similar 7-day rates of procedural success without ischemic complications (92% versus 93%; p = 0.53). More patients in the LP group had pre-dilation (72% versus 58%; p < 0.001) and post-dilatation (61% versus 50%; p = 0.001). The stent deployment pressure was significantly lower, as expected, in the LP group (10 2 ATM versus 13 4 atm; p < 0.001). At 30 days, the incidence of major adverse cardiac events was similar. At 6 months, the incidence of TVR was 10% and 7.8%, respectively (p = 0.28), hazard ratio was 0.79 (0.52 1.21), and absolute difference was 2.2% (-2.3% to 6.7%), well within the range of equivalency set at 7.5%. Patients without post-dilatation had a significantly higher rate of revascularization with the LP stent than with the Guidant stent (p = 0.02). Thus, the new LP stent achieves rates of revascularization that are not inferior to the Guidant stent, but this effect cannot be linked to lower-pressure deployment.
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PMID:A randomized multicenter trial comparing a new, low-pressure versus a conventional coronary stent: primary results from the CONSERVE trial. 1261 86


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