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

The development of drugs which block the renin-angiotensin system (RAS) has been proven a major advance in cardiovascular medicine. Angiotensin converting enzyme (ACE) inhibitors, which block the formation of angiotensin II from the inactive angiotensin I, are widely used as first line treatment in hypertension, heart failure and diabetic nephropathy. More recently, selective antagonists of the angiotensin type-1 receptor (AT1R) have become available for clinical use. Accumulating evidence suggests that AT1R antagonists have similar effects to ACE inhibitors in hypertension, heart failure and diabetic nephropathy. Although ACE inhibitors and AT1R antagonists block the same system, experimental evidence suggest that their mechanisms of action differ in several respects, such as increased bradykinin and angiotensin 1-7 levels with ACE inhibitors and AT2R activation with AT1R antagonists. Nevertheless, the clinical significance of these differences remains largely unknown and, in practice, the only clear advantage of AT1R antagonists over ACE inhibitors is the absence of cough as a side effect. Recent clinical data suggest that combined ACE inhibition and AT1R antagonism offer additive effects in reducing blood pressure in hypertension, in reducing proteinuria in nephropathy and in improving prognosis in heart failure. Further evidence suggests that some hypertensive patients may have a good antihypertensive response with ACE inhibition but not with AT1R antagonism, or the reverse. These data suggest that these two drug classes have important similarities, because they act on the same system, but they also appear to have important differences, which are not only of theoretical but also of clinical importance.
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PMID:Renin-angiotensin system blockade at the level of the angiotensin converting enzyme or the angiotensin type-1 receptor: similarities and differences. 1496 13

Hypertension is the major controllable risk factor associated with cardiovascular disease (CVD) events such as myocardial infarction, stroke, heart failure, and end-stage diabetes. A 5 mm Hg decrease in blood pressure has been equated with approximately 16% decrease in CVD. In the U.S. alone current annual antihypertensive drug costs are approximately dollars 15 billion. The renin-angiotensin-aldosterone system is a target for blood pressure control. Cleavage of angiotensinogen by renin produces angiotensin I which is subsequently hydrolyzed by angiotensin-I-converting enzyme (ACE) to angiotensin II (a potent vasoconstrictor). Various side effects are associated with the use of ACE inhibitory drugs in the control of blood pressure including hypotension, increased potassium levels, reduced renal function, cough, angioedema, skin rashes, and fetal abnormalities. Milk proteins, both caseins and whey proteins, are a rich source of ACE inhibitory peptides. Several studies in spontaneously hypertensive rats show that these casokinins and lactokinins can significantly reduce blood pressure. Furthermore, a limited number of human studies have associated milk protein-derived peptides with statistically significant hypotensive effects (i.e., lower systolic and diastolic pressures). The advent of effective milk protein based functional food ingredients/nutraceuticals for the prevention/control of blood pressure therefore has the potential to significantly reduce global healthcare cost.
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PMID:Hypotensive peptides from milk proteins. 1505 58

Angiotensin II plays a central role in the pathogenesis and progression of proteinuric nephropathies and related cardiovascular complications. Losartan is a selective non-peptide angiotensin Type 1-receptor blocker (ARB) with unique uricosuric effect, not shared by other ARBs. Losartan has demonstrated renoprotective effects in animals and humans with diabetic and non-diabetic renal diseases similar to those of angiotensin-converting enzyme inhibitors, with a lower incidence of dry cough and angioneurotic oedema. A reduced incidence of cerebrovascular events and diabetes has been reported in hypertensive patients with left ventricular hypertrophy on losartan therapy compared with patients treated with atenolol. Whether ARBs have superior cardioprotective effects, compared with other blood pressure medications, is still unknown. Combined angiotensin-converting enzyme inhibitor and ARB therapy improves renal outcomes in non-diabetic nephropathies more than single drug renin-angiotensin system inhibition. Whether this also applies to diabetic nephropathy and related cardiovascular outcomes is still unknown.
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PMID:Inhibition of the renin-angiotensin system and cardio-renal protection: focus on losartan and angiotensin receptor blockade. 1614 12

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.
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PMID:Clinical evidence for the cardiovascular benefits of angiotensin receptor blockers. 1696 48

Left ventricular (LV) dysfunction and/or heart failure (HF) are frequent complications of hypertension and myocardial infarction (MI), placing affected patients at increased risk of significant morbidity and premature death. Given that the renin-angiotensin-aldosterone system (RAAS) is activated and of pathophysiological importance in such patients, a strong therapeutic rationale exists to target the main effector mechanism (that is, angiotensin II [Ang II]) in order to lessen the associated morbidity and mortality burden. Angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce mortality and LV dysfunction and to slow disease progression in patients with HF, including high-risk, post-MI patients. However, ACE inhibitors (ACE-Is) may not provide optimal long-term RAAS blockade (a finding that is associated with a worse prognosis) and many patients are unable to tolerate such therapy (because of troublesome dry cough, for example). In contrast, Ang II receptor blockers (ARBs) may block the RAAS more completely than ACE-Is and appear to be better tolerated. Several large-scale trials gave evaluated the efficacy of ARBs in patients with LV dysfunction and/or HF (including high-risk, post-MI patients), and have confirmed their utility as an efficacious and well-tolerated alternative to ACE-Is in this setting.
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PMID:Use of valsartan in post-myocardial infarction and heart failure patients. 1698 31

Cecropia glaziovii Sneth is a common tree at the Southeastern Brazilian coast. As many other species of the genus, it shares the reputed folk use to treat heart failure, cough, asthma and bronchitis. The plant has been cultivated under controlled conditions and the 2% aqueous extract (AE) prepared with the dried leaves was standardized by its chemical contents on catechins, flavonoids and procyanidins. The present paper reports the antihypertensive activity of AE and of n-butanol fraction (BuF), an enriched semi-purified butanolic fraction used to isolate the main chemical constituents. Oral administration of AE and BuF induced hypotension in normotensive rats. The effect of AE (0.5 g/kg/bi, p.o.) was time and dose-dependent peaking at 2-3 weeks after daily administration. BuF was faster but not more active than AE. Both extracts decreased the hypertension of spontaneous hypertensive rats, the hypertension induced in rats by L-NAME treatment and that induced by constriction of one renal artery. The antihypertensive effect was maintained for as long as 60 days of treatment and was reversible upon drug washout at the same rate of its establishment. Acute i.v. administration of BuF to anesthetized rats induced a fast short-lasting hypotension and inhibited the pressor responses to noradrenaline, angiotensin I and angiotensin II by 40%. These results were indirect indications that the hypotension induced by AE is not related to ACE inhibition, increased NO synthesis, or specific blockade of alpha1 and AT1 receptors. It can be suggested that BuF interferes with the calcium handling mechanisms in smooth muscle cells and neurons. Intravenous injection of five out of nine compounds isolated from BuF produced immediate but short-lasting hypotension that does not correlate with the onset of the hypotension after oral treatment. This finding suggests that they may not be the compounds directly responsible for the delayed and sustained hypotension after per os administration of AE. The many compounds isolated from AE are under evaluation to determine its pharmacokinetics, mechanisms of action and interactions necessary to yield the plant effect. Although its mechanism is still unknown, AE seems to be an effective and safe antihypertensive phytomedicine.
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PMID:Antihypertensive effect of a standardized aqueous extract of Cecropia glaziovii Sneth in rats: an in vivo approach to the hypotensive mechanism. 1744 57

Imidapril (Tanatril), through its active metabolite imidaprilat, acts as an ACE inhibitor to suppress the conversion of angiotensin I to angiotensin II and thereby reduce total peripheral resistance and systemic blood pressure (BP). In clinical trials, oral imidapril was an effective antihypertensive agent in the treatment of mild to moderate essential hypertension. Some evidence suggests that imidapril also improves exercise capacity in patients with chronic heart failure (CHF) and reduces urinary albumin excretion rate in patients with type 1 diabetes mellitus. Imidapril was well tolerated, with a lower incidence of dry cough than enalapril or benazepril, and is a first choice ACE inhibitor for the treatment of mild to moderate essential hypertension.
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PMID:Imidapril: a review of its use in essential hypertension, Type 1 diabetic nephropathy and chronic heart failure. 1754 77

Hypertension is a common chronic disease that leads to significant cardiovascular morbidity and mortality worldwide. Blood pressure control is critical in reducing the end-organ complications, such as stroke, myocardial infarction, heart failure, or kidney disease. Currently available antihypertensive agents work by different mechanisms to reduce blood pressure. Aliskiren, a novel direct renin inhibitor, lowers blood pressure by decreasing renin activity, and angiotensin I and II levels. At the approved dosage (150-300 mg once daily), it reduces systolic blood pressure by 12-16 mm Hg and diastolic blood pressure by 2-12 mm Hg. In studies its efficacy was comparable to losartan 100 mg, irbesartan 150 mg, and valsartan 80-320 mg. When used adjunctively with ramipril, an angiotensin-converting enzyme (ACE) inhibitor, valsartan, an angiotensin II receptor blocker (ARB), or hydrochlorothiazide, a diuretic, it provides additional blood pressure reduction compared with placebo or monotherapy. Aliskiren is well tolerated, with the most common side effects being gastrointestinal symptoms, fatigue, weakness, and headache. In short-term clinical trials, aliskiren caused fewer disturbances in potassium levels when compared with hydrochlorothiazide, ACE inhibitors and ARBs. Long-term data on morbidity and mortality outcomes are not currently available, thus it is unknown whether aliskiren would join ACE inhibitors and ARBs as the preferred hypertensive agents for end organ protection. At this time, aliskiren should be considered as an alternative agent for mild-to-moderate hypertension, or as an adjunctive therapy when preferred agents fail to maintain optimal blood pressure control. It is also an option for those patients who have contraindications or intolerability to other antihypertensive agents, including dry cough induced by ACE inhibitors.
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PMID:Aliskiren: an oral renin inhibitor for the treatment of hypertension. 1809 68

Elevated blood pressure levels are highly prevalent and are a major reason for cardiovascular events and thus place a significant financial burden on healthcare systems worldwide. Guidelines recommend five first-line anti-hypertensive drug classes, but compelling indications may indicate favoring one drug class over another. Angiotensin receptor blockers (ARBs) have demonstrated a blood pressure lowering efficacy which is at least comparable with other drug classes, including ACE inhibitors (ACE-I), beta-blockers, calcium channel blockers and diuretics. They have, in addition, a lower side effect profile than other drug classes and patients on ARBs are more persistent with therapy. Compelling indications for the use of ARBs are heart failure, post-myocardial infarction, diabetic nephropathy, proteinuria/microalbuminuria, left ventricular hypertrophy, atrial fibrillation, metabolic syndrome and ACE-I induced cough. The ARB irbesartan has demonstrated a high efficacy in lowering blood pressure, which has been shown to be at least comparable with ACE-Is and superior to other ARBs such as losartan and valsartan. This translated into a better cost-effectiveness for irbesartan than for valsartan and losartan in the treatment of hypertension. In addition, irbesartan has been shown to be effective in both early and late stage diabetic nephropathy. It has further demonstrated considerable cost savings over standard therapy including beta-blockers, diuretics and non-dihydropyridine calcium channel blockers at all stages of kidney disease. Based on efficacy data from the Irbesartan Diabetic Nephropathy Trial and Reduction of Endpoints in NIDDM (non insulin dependant diabetes melitis) with the Angiotensin II Antagonist Losartan Study, it has also demonstrated cost savings over losartan in late stage renal disease. While both losartan and irbesartan are registered for the treatment of late stage diabetic nephropathy, irbesartan is also registered for early stage diabetic nephropathy in the EU. In summary, the data from randomized clinical trials on the efficacy of antihypertensive drugs provides an indication of their real value to patients. In addition observational data from clinical practice and proven end-organ protection in diabetic nephropathy provides further evidence of the true value of irbesartan compared to other ARBs in the treatment of hypertension.
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PMID:The value of irbesartan in the management of hypertension. 1960

The renin angiotensin system (RAS) plays an important role in regulation of blood pressure and fluid-electrolyte homeostasis. The renin-angiotensin system consists of a cascade of enzymatic reactions producing angiotensin II (Ang II). Ang II is a vasoconstrictive peptide hormone that exerts a wide variety of physiological actions on cardiovascular, renal, endocrine and central nervous systems. The RAS can be inhibited at various points to control pathogenesis of hypertension. Renin inhibitors and angiotensin-converting enzyme (ACE) inhibitors were the earliest RAS blocking agents. A relatively new class of compounds known as Ang II receptor antagonists (SARTANs) is developed for the treatment of hypertension. They exert their action by blocking the binding of Ang II on AT(1) receptor. Angiotensin converting enzyme (ACE) inhibitors are associated with incident of side effects such as cough and angioedema while clinical trials with Ang II receptor antagonists have confirmed that these drugs are safe and efficacious for the treatment of hypertension. Based upon the understanding of molecular interaction of Ang II receptor antagonists with AT(1) receptor some of the common structural features have been identified, such as a heterocyclic (nitrogen atom) ring system, an alkyl side chain and an acidic tetrazole group. Research efforts for development of new molecules with similar structural features have led to the discovery of various non-peptidic Ang II receptor antagonists with different substituted heterocyclic such as imidazole (losartan) and benzimidazole (candesartan and telmisartan). In this study we have critically reviewed various benzimidazole substituted compounds as Ang II-AT(1) receptor antagonists and explored other potential clinical uses for this class of compounds.
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PMID:Substituted benzimidazole derivatives as angiotensin II-AT1 receptor antagonist: a review. 2093 29


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