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)

Central administration of AT1 receptor blockers prevents salt-sensitive hypertension and inhibits progression of CHF. We investigated in Wistar rats the effectiveness of peripheral administration of two AT1 receptor blockers, losartan and embusartan, in exerting central AT1 receptor blockade. Losartan or embusartan at doses of 30 and 100 mg/kg were administered subcutaneously (s.c.) as a single dose, or one dose daily for 6 days. The BP responses to intracerebroventricular (i.c.v.) injection of Ang II, i.c.v. infusion of Na+-rich aCSF (0.3 M NaCl), and intravenous (i.v.) injection of Ang II were then measured. Losartan or embusartan at 30 and 100 mg/kg both inhibited the BP increases induced by i.c.v. Ang II and, to a lesser extent, by Na+-rich aCSF. After a single dose, this inhibition was more pronounced for losartan. However, after 6 days of treatment, there were no significant differences between the effects of losartan and embusartan. Losartan and embusartan blocked responses to Ang II i.v. to a similar extent. These results indicate that results from single-dose studies may not reflect the chronic steady-state, and that during chronic treatment both AT1 receptor blockers are similarly effective in inhibiting AT1 receptors in the central nervous system, when assessed by pressor responses to acute increases in CSF Na+ or CSF Ang II.
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PMID:Peripheral administration of AT1 receptor blockers and pressor responses to central angiotensin II and sodium. 1169 45

Activation of the renin-angiotensin-aldosterone system is associated with unsatisfactory outcomes in patients with hypertension and congestive heart failure, in that activation of this system is correlated strongly with both the incidence and extent of end-organ damage. Despite the availability of the angiotensin-converting enzyme inhibitors and the AT1 receptor antagonists, unblocked aldosterone levels remain an important risk factor for cardiovascular disease progression. New preclinical data generated over the past few years strongly support the hypothesis that aldosterone has important deleterious effects on the cardiovascular system independent of the classical action of this hormone on renal epithelial cells. The new selective aldosterone receptor antagonist eplerenone has been shown to produce significant cardioprotective effects in experimental models of cardiovascular disease. Early clinical testing suggests that eplerenone may have important therapeutic benefit in the treatment of hypertension and heart failure.
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PMID:Recent studies with eplerenone, a novel selective aldosterone receptor antagonist. 1171 95

Medical therapy for chronic heart failure has recently been extensively revised on the basis of a reduction of mortality in randomized trials. However, there are almost no available trials in children whose treatment for heart failure is adapted from what is known in adults. Digitalis play a role in heart rate variability but there is no evidence for an effect on mortality. Angiotensin-converting enzyme inhibitors lead to an improvement of left ventricular function and reduces mortality; in addition, they are well tolerated in children. Diuretics are useful in congestive heart failure but chronic administration may have deleterious effects. Beta-blocking agents reduce mortality and improve symptoms and the ejection fraction; however, they must be given cautiously and the up-titration phase must be very progressive. New promising drugs are emerging (calcium sensitizers, phosphodiesterase inhibitors, angiotensin receptor [AT1] blockers) but at the present time their use in chronic heart failure has not proven to be efficient.
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PMID:[Treatment of chronic heart failure in the child]. 1181 Oct 37

Angiotensin II is the effector peptide of the renin-angiotensin system and is involved in a wide range of physiologic functions that relate to volume control. In this regard, angiotensin II maintains and regulates salt and water balance, is critically involved in cardiovascular function, and governs thirst. When present in excess, angiotensin II can pathologically influence each of these functions. The role of angiotensin II in controlling sodium balance, in both renal insufficiency states and congestive heart failure, is clearly recognized. Alternatively, it is poorly appreciated that angiotensin II plays an important role in both normal and pathologic thirst states. The latter is a potential problem in both end-stage renal disease and congestive heart failure. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor antagonists (AT1-RAs) have both been shown to reduce abnormal thirst drive. Whether an ACE inhibitor or an AT1-RA lessens thirst drive to any significant degree relates to its capacity to penetrate the blood-brain barrier. Head-to-head comparisons of ACE inhibitors and AT1-RAs, as to their effect on thirst drive, have not been undertaken in a systematic fashion; thus, until otherwise established, the effect of these compounds on thirst should be viewed as a class effect, albeit one that is likely to be dose-dependent. (c)2001 CHF, Inc.
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PMID:Pharmacotherapy in congestive heart failure: angiotensin II and thirst: therapeutic considerations. 1182 79

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

Chronic pharmacotherapy of congestive heart failure deals with its special pathophysiology and acts on different sites of the cardiorenal axis. The standard-therapy consists of diuretics, ACE-inhibitors and beta-blockers and can be supplemented by cardiac glycosides, if heart failure worsens. Cardiac glycosides are also administered if tachycardic arrhythmias occur. Aldosterone-antagonists are combined with standard therapy in NYHA III - IV to counteract cardiac remodelling. AT1-antagonists are indicated when ACE-inhibitors are contraindicated or cannot be administered because of side-effects. Combination with ACE-inhibitors and AT1-antagonists may be of benefit for the patient since morbidity and hospitalization decrease.
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PMID:Pharmacotherapeutic strategy in heart failure. 1222 21

The congestive heart failure is a pathological process characterized by the incapacity of the heart to maintain an adequate cardiac perfusion for the tissue metabolism, and that can be secondary to diverse causes, that give as result, alterations in the lusitropism, inotropism or in the cronotropism. Over 4.6 persons per hundred in the United States alone carry this diagnosis, and it is the cause of death in several hundred thousand patients each year, with a 35% mortality over 5 years. In the last years, have existed important advances in the pharmacological treatment of this disease in it's terminal stages. The increase in the knowledge on the physiopathology of the heart failure, has taken place for the use of new schemes of treatment, where it excels the use of vasoactive amines, Angiotensin Converting Enzyme Inhibitors, angiotensin II receptor AT1 antagonists, etc; nevertheless we whereupon that most of these drugs that at the present display a favorable answer to the disease, has the disadvantage of increasing the consumption of oxygen by the own myocardium tissue. Levosimendan has a better profile of security than its predecessors (amrinone and milrinone), improves the haemodynamics parameters of special significant form in the cardiac output, the systolic pressure of the pulmonary artery and the telediastolic pressure of the left ventricle, without significantly increasing the consumption of oxygen by the myocardium. Levosimendan is a new and relevant calcium sensitizer developed for the short-term intravenous treatment of congestive heart failure.
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PMID:[Levosimendan: a new option in the pharmacologic management of cardiac insufficiency]. 1266 17

In congestive heart failure, renal blood flow is decreased and renal vascular resistance is increased in a setting of increased activity of both the sympathetic nervous and renin-angiotensin systems. The renal vasoconstrictor response to renal nerve stimulation is enhanced. This is associated with an abnormality in the low-pass filter function of the renal vasculature wherein higher frequencies (> or =0.01 Hz) within renal sympathetic nerve activity are not normally attenuated and are passed into the renal blood flow signal. This study tested the hypothesis that excess angiotensin II action mediates the abnormal frequency response characteristics of the renal vasculature in congestive heart failure. In anesthetized rats, the renal vasoconstrictor response to graded frequency renal nerve stimulation was significantly greater in congestive heart failure than in control rats. Losartan attenuated the renal vasoconstrictor response to a significantly greater degree in congestive heart failure than in control rats. In control rats, the frequency response of the renal vasculature was that of a first order (-20 dB/frequency decade) low-pass filter with a corner frequency (-3 dB, 30% attenuation) of 0.002 Hz and 97% attenuation (-30 dB) at > or =0.1 Hz. In congestive heart failure rats, attenuation did not exceed 45% (-5 dB) over the frequency range of 0.001-0.6 Hz. The frequency response of the renal vasculature was not affected by losartan treatment in control rats but was completely restored to normal by losartan treatment in congestive heart failure rats. The enhanced renal vasoconstrictor response to renal nerve stimulation and the associated abnormality in the frequency response characteristics of the renal vasculature seen in congestive heart failure are mediated by the action of angiotensin II on renal angiotensin II AT1 receptors.
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PMID:Losartan corrects abnormal frequency response of renal vasculature in congestive heart failure. 1282 30

Congestive heart failure (CHF) is characterised by activation of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system (SNS). Both systems are known to interact and to potentiate each other s activities. We recently demonstrated that angiotensin II (Ang II) enhances sympathetic nerve traffic via prejunctionally-located AT1-receptors. At present, little is known about the effects of Ang II at the level of the sympathetic neurones in CHF. Accordingly, we investigated the effect of Ang II in the presence and absence of the AT1-receptor antagonist, eprosartan, on stimulation-induced nerve traffic in isolated thoracic aorta preparations obtained from rabbits suffering from experimentally-induced CHF. Control-preparations were obtained from age-matched animals. Sympathetic activity was assessed by a [3H]noradrenaline spill-over model. Additionally, Ang II constrictor responses were compared between CHF and control vessels in the presence and absence of eprosartan. Additionally, to study postjunctional facilitation, the effects of Ang II on postsynaptic a-adrenoceptor-mediated responses were studied using noradrenaline. Stimulation-evoked SNS-neurotransmission was similar in both groups (CHF versus control). Ang II (0.1 nM 0.1 M) caused a concentration-dependent increase of the stimulation-evoked sympathetic outflow in both groups, with a maximum at 10 nM (control [n=7], FR2/FR1 2.03+0.11 and CHF- preparations [n=7], FR2/FR1 1.71+0.07). The enhancement by Ang II was decreased in CHF- preparations compared with controls (p<0.05). Eprosartan concentration-dependently attenuated the Ang II-enhanced (10 nM) sympathetic outflow in both CHF- and control preparations. The sympatho-inhibitory potency of eprosartan was similar in both groups (control pIC50 8.81 0.31; CHF 8.65+0.42). Ang II (1 nM 0.3 M) concentration-dependently increased the contractile force in control preparations (Emax 21.64+3.86 mN, pD2 7.63+0.02, n=7). Eprosartan (1 nM 0.1 M) influenced the Ang II- contractions via a mixed form of antagonism. In CHF-preparations, Ang II caused impaired vascular contraction. The KCl-induced contraction was decreased in the CHF- compared with control preparations (13.02+0.64 mN versus 30.40+0.89 mN). The relative Ang II contraction (% of KCl) was also decreased (2.3% vs. 58.0%). Concentration-response curves to noradrenaline (%KCl) were similar (control pD2 6.93+0.05, Emax 131.0+2.7; CHF pD2 7.00+0.05, Emax 136.7+2.6) (p>0.05) and were not affected by Ang II. We conclude that Ang II-enhanced sympathetic neurotransmission is mediated by the prejunctional AT1-receptor in both control and CHF-preparations. The decreased facilitation of SNS effects by Ang II may be explained by down-regulation or desensitisation of the neuronal AT1-receptor. Additionally, the aortic contractile capacity in heart failure rabbits appears to be decreased, probably as a result of heart failure-associated neuroendocrine and functional changes.
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PMID:Impaired neuronal and vascular responses to angiotensin II in a rabbit congestive heart failure model. 1468 69

The angiotensin II receptor blockers (ARBs), are highly selective for the AT1 subtype and will block the effects of angiotensin II on peripheral vessels. Several short- and long-term studies have shown these agents to be safe and effective antihypertensive drugs. Since monotherapy of hypertension may be ineffective in lowering the blood pressure to goal, the use of an ARB, especially in combination with a diuretic or another medication, is frequently necessary to bring the blood pressure <140/90 mm Hg (<130/80 mm Hg among people with diabetes mellitus or chronic renal failure), according to JNC 7 guidelines. Besides hypertension, the ARBs have been shown to reduce left ventricular hypertrophy in hypertensive patients. Other benefits of these medications, as well as the angiotensin I converting enzyme inhibitors (ACEIs), include a decrease in cardiovascular morbidity and mortality in patients with heart failure, or hypertensive diabetic nephropathy with proteinuria. Some of the beneficial effects noted with the ACEIs and ARBs (congestive heart failure, left ventricular hypertrophy), have also been demonstrated with the use of b blockers alone and in combination with a diuretic. These drugs, i.e., b blockers, ARBs, and ACEIs, seem to exert their beneficial action through the blockade of the renin-angiotensin-aldosterone system. The role of this system in cardiovascular remodeling and its blockade will be discussed in this review, which will specifically summarize data with the ARB, valsartan.
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PMID:Clinical experience with angiotensin receptor blockers with particular reference to valsartan. 1530 83


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