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Query: UMLS:C0010200 (cough)
 23,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As a net effect of ACE-inhibitors and AT1-receptor antagonists on the renin-angiotensin system (RAS) cardioprotection due to vasodilative (reduction of blood pressure, afterload reduction), antiproliferative (reduced cell growth, reduction of "vascular" and/or "ventricular remodeling", reduced formation of extracellular matrix), as well as antiadrenergic actions and due to the stimulating effect on natriuresis, reduction of blood pressure, preload reduction can be expected. These aims of therapy have mostly been confirmed for the action of ACE-inhibitors by experimental and clinical studies but except for the treatment of arterial hypertension and few preliminary reports concerning the treatment of cardiac dysfunction, no comparable data are available for AT1-receptor antagonists. To date, an antithrombotic and profibrinolytic action could only be demonstrated for ACE-inhibitors. This effect has been discussed to be responsible for the improvement of long-term prognosis in patients with coronary artery disease. Despite the similar spectrum of action there exist important differences between ACE-inhibitors and AT1-receptor antagonists that might underline the need of an individual use of these drugs: the dual action of ACE-inhibitors on the RAS and the kinin system bears many benefits but has been also shown to be accompanied by side-effects, mainly chronic dry cough, in a relatively high percentage of patients thus leading to discontinuation of therapy in 8-14%. This respective side-effect can be prevented by the use of AT1-receptor antagonists. It has been discussed whether the incomplete action of ACE-inhibitors on AT1-receptor-mediated effects is at least in part responsible for the efficacy of this drug which is relatively high (75-80%) as compared to other substances. Due to their direct action, AT1-receptor-blockers might also be of high effectiveness for the treatment of severe heart failure. A combination of the ACE-inhibitor-mediated activation of the kinin-system with the more specific blockade of AT1-receptors by AT1-receptor antagonists might be of benefit and is currently under investigation. Finally, it has been discussed that the increased AT II concentration in case of AT1-receptor-blockade activates AT2-receptor-mediated mechanisms thus leading to an additive vasoprotective effect.
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PMID:[Pathophysiological mechanisms of the renin-angiotensin system and its pharmacologic modification by ACE inhibitors or angiotensin II (type 1) receptor blockers in cardiovascular diseases]. 923 95

The octapeptide hormone, angiotensin II, binds to two major subtypes of cell surface receptors: the AT1 and the AT2 angiotensin receptors. The important physiological and pathophysiological effects of angiotensin II on cardiovascular regulation and salt-water balance are mediated by the AT1 receptor subtype. As a consequence of the outstanding clinical success of angiotensin-converting enzyme inhibitors, the appearance of AT1 receptor inhibitors in the therapy of hypertension and other cardiovascular diseases was preceded with great expectations. The available experimental and clinical data indicate that the first AT1 receptor inhibitor, losartan, has the same therapeutic potential as angiotensin-converting enzyme inhibitors, but it does not evoke the angiotensin-independent side-effects of ACE inhibitors, such as dry cough or angioedema. The physiological importance and the biochemical, molecular biological and pharmacological properties of AT1 and AT2 receptors are reviewed in this paper, and a summary of the available clinical data is presented.
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PMID:[AT1 angiotensin receptor inhibition as a new therapeutic possibility]. 941 27

Angiotensin (Ang) II antagonists provide specific and selective blockade of Ang II at the AT1 receptor, regardless of the enzymatic pathway of production. Valsartan has an affinity for the AT1 receptor 30,000 times that of the AT2 receptor. Valsartan is not a prodrug and undergoes little metabolism. It has a half-life of approximately 9 h, but duration of antihypertensive action at the usual dose of 80 or 160 mg daily is 24 h. The trough to peak ratio is 0.66. Valsartan has antihypertensive efficacy at least equivalent to that of established antihypertensive drugs and has additive effects in combination. The efficacy of valsartan appears to be independent of age, sex, and race. Valsartan is effective in hypertensive patients with renal insufficiency and is associated with maintenance of renal function. It is well tolerated, with a side-effect profile indistinguishable from that of placebo, and does not cause cough. Ang II antagonists are a promising class of cardiovascular drugs with considerable potential in clinical practice.
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PMID:Angiotensin II antagonism in clinical practice: experience with valsartan. 1002 51

Angiotensin II type 1 (AT1) receptor blockers, such as candesartan, are attractive alternatives to ACE inhibitors in the treatment of hypertension and cardiovascular disease. Although angiotensin-converting enzyme (ACE) inhibitors are able to suppress the renin-angiotensin system (RAS), their mechanism of action may limit their clinical utility in the treatment of hypertension. For example, they act as competitive inhibitors of ACE. This means that their effects can be overcome by high levels of angiotensin I, which occur after ACE inhibition due to removal of the negative feedback effect of angiotensin II on renal renin release. ACE inhibitors are also unable to block the production of angiotensin II by non-ACE-mediated pathways. Furthermore, ACE is not a specific enzyme. Its inhibition therefore has effects on other substances, such as bradykinin, leading to the class-specific side effects associated with ACE inhibitors. Candesartan, on the other hand, binds insurmountably to the AT1-receptor, thereby providing more complete blockade of the negative cardiovascular effects of angiotensin II than is possible with ACE inhibitors. The specificity of AT1-receptor blockade also ensures that efficacy is achieved without inducing the side effect of cough that results from the non-specific consequences of ACE inhibition. Preclinical and early clinical studies demonstrate that AT1-receptor blockers produce at least the same degree of target-organ protection as has been demonstrated for ACE inhibitors. Additional benefits of AT1-receptor blockers may arise from the fact that, unlike ACE inhibitors, they do not prevent the activity of angiotensin II on AT2-receptors in the heart, which is thought to reduce cardiac remodelling. From a mechanistic perspective, therefore, AT1-receptor blockers appear to have advantages over ACE inhibitors, in terms of a more complete blockade of angiotensin II effects, while also avoiding the specific side effects associated with ACE inhibition.
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PMID:Angiotensin II type 1 receptor blockade: a novel therapeutic concept. 1105 29

The A II antagonists (RA II antagonists) are a new group of anti-hypertensive drugs with five years of clinical use. They were investigated after the knowledge of independent ways to get angiotensin II. They block AT1 receptor. It's possible that, after AT1 block, the high plasmatic levels of AII stimulate the AT2 receptors with vasodilation and anti-proliferative activity. We are waiting for the results of several big prospective studies with RA II antagonists on cardiovascular morbidity and mortality. At present time, the first indication for its use is the appearance of cough when taking ACE inhibitors. The association of ACE inhibitors and RA II antagonists can improve some clinical conditions like dilated hypertensive cardiopathy, nephropathy or refractory hypertension.
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PMID:[ACE inhibitors versus AR II antagonists. Their role in arterial hypertension]. 1130 10

Angiotensin II(AII) accelerates the progress of cardiovascular diseases. This was proved by the fact that the blockade of renin-angiotensin system provided clinical benefits for patients with cardiovascular diseases. This review focuses on the differences between AT1-receptor antagonist and ACE inhibitor in basic and clinical aspects. Beside decreased AII concentration, increased tissue bradykinin concentration may contribute to the beneficial effect of ACE inhibitor, on the other hand, this increases the rate of cough to decrease the compliance. Increased AII concentration by AII receptor antagonist may antagonize the binding of the drug as well as stimulate AT2 receptor subtype. ACE inhibitor can not block the effect of non-ACE AII formation, but AII receptor does. These differences should be considered for their clinical use.
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PMID:[Comparison between AngII receptor antagonist and ACE inhibitor]. 1139 5

Blockade of the renin-angiotensin system (RAS) is now recognised as an effective approach for the treatment of hypertension and congestive heart failure (CHF). Today, it is possible to antagonise the effects of angiotensin II more specifically by blocking its receptors using non-peptide receptor antagonists. These compounds, which at first were used to identify the various subtypes of angiotensin II receptors, are now available clinically. Some of them have recently been launched on the market and several others are preregistered for the treatment of hypertension. These new molecules are as effective as angiotensin converting enzyme (ACE) inhibitors at lowering blood pressure in hypertensive patients, and appear to have similar systemic and renal haemodynamic properties in patients with CHF and renal diseases. Large-scale clinical trials such as the LIFE, the ELITE and the RENAAL studies are now underway to investigate the long-term benefits of one of these agents in hypertension, heart failure and Type II diabetic nephropathy. The major clinical advantage of AT1 receptor antagonists is that, in contrast to ACE inhibitors, they do not induce cough. With the more widespread use of AT1 receptor antagonists, two unresolved questions remains unanswered: what is the role of AT2 receptors? Are the unblocked effects of angiotensin II on AT2 receptor sites of any clinical relevance to the safety profile or efficacy of AT1 receptor antagonists? Another interesting question is whether the combination of an ACE inhibitor with an AT1 receptor antagonist is advantageous. Studies attempting to answer these questions are underway and will certainly enable researchers to define more precisely the role and the advantages of these new specific non-peptide AT1 receptor antagonists in the treatment of hypertension and heart failure.
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PMID:Angiotensin II receptor antagonists - antihypertensive agents. 1598 15

The renin-angiotensin-aldosterone-system (RAAS) is an important regulator of blood pressure and fluid-electrolyte homeostasis. RAAS has been implicated in pathogenesis of hypertension, congestive heart failure, and chronic renal failure. Aliskiren is the first non-peptide orally active renin inhibitor approved by FDA. Angiotensin Converting Enzyme (ACE) Inhibitors are associated with frequent side effects such as cough and angio-oedema. Recently, the role of ACE2 and neutral endopeptidase (NEP) in the formation of an important active metabolite/mediator of RAAS, ang 1-7, has initiated attempts towards development of ACE2 inhibitors and combined ACE/NEP inhibitors. Furukawa and colleagues developed a series of low molecular weight nonpeptide imidazole analogues that possess weak but selective, competitive AT1 receptor blocking property. Till date, many compounds have exhibited promising AT1 blocking activity which cause a more complete RAAS blockade than ACE inhibitors. Many have reached the market for alternative treatment of hypertension, heart failure and diabetic nephropathy in ACE inhibitor intolerant patients and still more are waiting in the queue. But, the hallmark of this area of drug research is marked by a progress in understanding molecular interaction of these blockers at the AT1 receptor and unraveling the enigmatic influence of AT2 receptors on growth/anti-growth, differentiation and the regeneration of neuronal tissue. Different modeling strategies are underway to develop tailor made molecules with the best of properties like Dual Action (Angiotensin And Endothelin) Receptor Antagonists (DARA), ACE/NEP inhibitors, triple inhibitors, AT2 agonists, AT1/TxA2 antagonists, balanced AT1/AT2 antagonists, and nonpeptide renin inhibitors. This abstract gives an overview of these various angiotensin receptor antagonists.
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PMID:An update on non-peptide angiotensin receptor antagonists and related RAAS modulators. 1769 38

Heart Failure (HF) is a progressive and fatal disorder, which ranks among the major public health problems in Brazil and worldwide. However, survival for patients who developed the syndrome after myocardial infarction (MI) enhanced significantly, as a result of an improvement of pharmacological therapies. A medical breakthrough was the discovery that remodelling of the left ventricle (LV) may be limited by the blockade of the renin-angiotensin system (RAS), at the level of angiotensin converting enzyme (ACE) and binding of angiotensin (Ang) II to its AT1 receptor. This review shows that the therapeutic effects of both ACE inhibitors and the angiotensin receptor blockers (ARB) go beyond the interference in the biochemical pathway ACE-Ang II AT1-receptor. Such effects are also related to the potentiation of bradykinin and increased beneficial effects mediated by the AT2 receptor. Therefore, the results of five randomized trials were presented, which evaluated the use of losartan, valsartan or candesartan, considering their effects on survival and risk of clinical deterioration in patients with symptomatic HF after MI. These studies confirmed the advantage of ARBs over inhibitors in case of cough, rashes and angioneurotic edema, despite similar adverse effects, such as hyperkalemia, renal failure and hypotension. Thus, in this article we have discussed with patents that ACE inhibitors also appear as the first option as RAS inhibitors in search of relevant results for the patient, allowing the alternative use of ARBs to those patients with intolerance.
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PMID:Blockade of renin angiotensin system in heart failure post-myocardial infarction: what is the best therapy? 2499 97