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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After a brief synopsis of the classical antihypertensive drugs a survey is given of the newer therapeutics, such as calcium antagonists, ACE-inhibitors and alpha 1-adrenoceptor antagonists. Experimental drugs, such as imidazoline receptor agonists, renin inhibitors, angiotensin II receptor antagonists, alpha 2-adrenoceptor antagonists, potassium channel openers, ketanserin, endopeptidase inhibitors, and hybrid (multifactorial) drugs are discussed, with special attention for their modes of action. In spite of the ever increasing number of antihypertensive drugs and principles, the large scale of clinical evidence for a beneficial effect of long-term treatment (in particular with respect to protection against stroke) remains limited to diuretics and beta-blockers. In spite of this limitation it seems worthwhile to consider the newer antihypertensive drugs as well, especially for optimal treatment of the individual patient. The newer drugs may in particular offer special advantages in the presence of concomitant diseases, such as diabetes mellitus, hyperlipidaemia, angina pectoris or congestive heart failure.
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PMID:New avenues in antihypertensive drug treatment. 826 86

Over the last 40 years effective drug treatment of hypertension has become available. Newer classes of drugs offer efficacy with simplicity of dosing regimen and good patient acceptability. However, there is increasing interest in the long-term benefits of treatment, particularly influences on total mortality and morbidity and mortality from coronary artery disease and its complications. Established treatments with diuretics and beta blockers do reduce stroke risk but have less than predicted effects on coronary heart disease. While there is experimental evidence and clinical pointers that ACE inhibitors and calcium antagonists may influence atherosclerosis in the long-term, there is as yet no objective clinical confirmation. The aim of treatment in the 1990s is to control blood pressure (and other risk factors) in the short-term with a view to improving long-term outcome. Many clinicians have modified step-care approaches to individualize drug treatment using one or two agents, selected from older and newer classes, which on clinical grounds are most appropriate in the individual patient. Factors determining choice are race, other risk factors and associated diseases.
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PMID:Drug treatment of hypertension. 836 Nov 33

Neuropeptide Y (NPY) is a peptide released together with noradrenaline (NA) from sympathetic nerve endings. Elevated plasma levels of NA and NPY-like immunoreactivity (LI) are found in patients with congestive heart failure. In order to assess any relationship found between plasma NPY-LI and haemodynamic data 12 patients with mild to moderate chronic congestive heart failure were studied during cardiac catheterization. All patients were treated with diuretics but not ACE inhibitors and were in New York Heart Association functional class II or III. Mean left ventricular ejection fraction determined by echocardiography was 34%. Plasma NPY-LI from mixed venous blood was elevated in five patients and NA in nine. Mean plasma NPY-LI was 29 +/- 3 pmoll-1 (mean +/- standard error of the mean) and NA 2.6 +/- 0.3 nmoll-1. Heart rate was 70 +/- 3 beats min-1, systolic blood pressure (SBP) 131 +/- 7 mmHg, stroke volume index (SVI) 29 +/- 1.9 ml m-2 and cardiac index (CI) 2.0 +/- 0.13 l min-1 m-2. Elevated levels of plasma NPY-LI (> 30 pmol l-1) were associated with lower SVI, CI, and SBP and a higher pulmonary vascular resistance. Elevated plasma NA (> 2 nmol l-1) did not correlate with haemodynamic data. Log NPY-LI correlated inversely with SVI (P < 0.01) and CI (P < 0.05) but not with plasma NA. It is concluded that log NPY-LI in mixed venous blood correlates inversely with SVI and CI in patients with mild to moderate chronic congestive heart failure.
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PMID:Neuropeptide Y, noradrenaline and invasive haemodynamic data in mild to moderate chronic congestive heart failure. 837 Feb 39

Keeping pre-transplant patients alive while waiting for a suitable donor is still a major challenge. New pharmacological agents which can provide improved hemodynamics are urgently needed in patients with severe heart failure who are on the waiting list for cardiac transplantation. Intravenous enoximone therapy (an initial 0.5 mg/kg bolus, then 1.25-5.0 mcg/kg/min infusion) was administered to 35 transplant candidates with progressive heart failure despite optimal drug regimen including digoxin, diuretics, and ACE-inhibitors. In 18 out of 35 patients complete hemodynamic, echocardiographic, neurohumoral, and Holter-ECG studies were performed before and 24 hours after intravenous enoximone infusion. Patients were then continued on chronic oral therapy of 100 mg twice a day. Enoximone infusion increased the cardiac index (CI) (1.78 +/- 0.45 l/min/m2 vs 3.04 +/- 0.83 l/min/m2; p < 0.001) and stroke volume index (SVI)(22.33 +/- 9.45 ml/m2 vs 32.28 +/- 7.29 ml/m2; p < 0.05) and decreased wedge pressure (PCP)(24.1 +/- 11.98 mmHg vs 17.78 +/- 8.76 mmHg; p < 0.05) while mean arterial pressure (MAP) was unchanged. Left ventricular ejection time (LVET)(225.1 +/- 26.9 ms vs 242.2 +/- 25.8 ms; p < 0.05) was increased whereas other echocardiographic parameters were unchanged (Left ventricular end-diastolic dimension LVEDD, left ventricular end-systolic dimension LVESD, fractional shortening FS, early diastolic relaxation parameter Te). Plasma neurohumoral parameters did not change (Aldosterone, epinephrine, renin, atrial natriuretic factor) except for a significant drop in norepinephrine (936.7 +/- 443.2 pg/ml vs 522.4 +/- 287.6 pg/ml; p < 0.05). Holter-ECG parameters (ventricular premature beats VPB, couplets, ventricular tachycardia VT) were not influenced by enoximone infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enoximone therapy as pharmacological bridging to cardiac transplantation. 837 84

To determine the effect of ACE inhibitor therapy on lymphocyte beta-adrenoceptor function and density, as well as the in vivo myocardial response to beta-agonist stimulation, we studied 12 patients with chronic severe heart failure before and after 16 weeks' treatment with quinapril. Lymphocyte beta-adrenoceptor function (intracellular cAMP production in response to isoprenaline) was studied as a surrogate tissue for myocardium, and increased significantly after quinapril at concentrations of isoprenaline between 10(-3) and 50 mmol.l-1. Lymphocyte beta-adrenoceptor density (six patients) measured by [125I] iodocyanopindolol binding, increased from 242 +/- 72 (mean +/- SEM) to 884 +/- 17 receptors/cell (P < 0.05). Changes in functional myocardial beta-adrenoceptor status were determined by measuring changes in haemodynamic responses to exercise and to incremental dobutamine infusion. Following quinapril there were significant improvements in cardiac index, stroke volume and cardiac power output during sub-maximal exercise testing and dobutamine infusion; stroke work index in response to dobutamine (but not exercise) improved significantly. ACE inhibitors cause lymphocyte beta-adrenoceptor upregulation in heart failure, which is associated with an improved cardiac pumping capacity in response to beta-agonist stimulation.
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PMID:Lymphocyte beta adrenoceptor upregulation and improved cardiac response to adrenergic stimulation following converting enzyme inhibition in congestive heart failure. 838 98

Thiazide diuretics have been the mainstay of antihypertensive therapy for over 30 years. Their precise mechanism of antihypertensive action is still incompletely understood. They reduce arterial pressure initially through a fall in plasma volume and cardiac output. However, with chronic administration cardiac output tends to return toward pretreatment levels, suggesting that the long-term pressure reduction is mediated through a reduction in vascular resistance. Although multiple lines of evidence suggest that salt and water loss is an essential part of the mechanism, at least in some cases an indirect vasodilator effect may play a role as well. The antihypertensive efficacy of diuretics is proven; they are at least as effective as other classes of antihypertensive drugs. They have been shown to protect against stroke, but not against mortality from myocardial infarction. There is some concern about the metabolic side effects, such as hypokalemia, hyperglycemia, and hyperlipidemia. In order to minimize these side effects the lowest effective dose should be used. Diuretics are likely to remain first-line antihypertensive agents, but they should be considered as one of several possible choices for the initial therapy among other classes, such as beta-blockers, ACE inhibitors, or calcium entry blockers.
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PMID:The place of diuretics in the treatment of hypertension: a historical review of classical experience over 30 years. 843 77

Antihypertensive treatment with diuretics and/or beta-blockers lowers stroke and coronary heart disease morbidity and mortality. However, although the newer antihypertensives induce effective control of blood pressure and regression of hypertensive organ damage, it has not been proven whether they reduce mortality. Ongoing clinical trials such as STOP II, CAPPP, NORDIL, INSIGHT, ALLHAT and LIFE test whether antihypertensive regimens with ACE-inhibitor, calcium-blocker, alpha-blocker and Angiotensin II-antagonist are equally good or possibly even better than diuretics and beta-blockers in preventing cardiovascular complications. The HOT trial clarifies how much the diastolic blood pressure should be lowered, and whether a small dose of aspirin has a protective effect when combined with optimal control of blood pressure. These studies should give better guidelines for the treatment of hypertension.
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PMID:[Status of ongoing controlled clinical trials on hypertension]. 1535 9

The development of hypertension is associated with the presence of cardiovascular structural alterations. The principal target organs of hypertensive disease are the heart, brain, kidney and eye. Although left ventricular hypertrophy is an initially useful and well tolerated adaptive mechanism because it tends to reduce wall stress, it may subsequently lead to impaired cardiac function and even heart failure. Vascular structural alterations include reduced compliance, the appearance of atheromatous lesions in the large arteries, and hypertrophy or remodelling of small artery walls, and may be involved in the onset of retinal, renal and brain lesions. Technological progress now enables us to evaluate cardiovascular structural alterations early on as well as to monitor their natural history and the modifications induced by antihypertensive therapy. There is no question as to capacity of antihypertensive therapy to reduce the incidence of stroke, heart failure, renal failure and severe hypertensive retinopathy. Although a number of drugs are able to lower blood pressure, ACE-inhibitors and calcium entry blockers more effectively bring about the regression of left ventricular hypertrophy and, probably, also the retrocession of structural alterations in small resistance arteries; they seem to have a beneficial effect on structural alterations in large arteries as well. Although the regression of left ventricular hypertrophy could be associated with an improved prognosis, no data are available yet on the prognostic significance of the presence and regression of vascular structural alterations.
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PMID:[The organ damage in arterial hypertension]. 856 78

The 'discovery' of losartan represents three separate discoveries: (1) losartan as the unique biphenyltetrazole molecule and the first of a new chemical class; (2) losartan as a tool to identify AT1-subtype receptors; and (3) losartan as a specific probe for exploring the multiple roles of angiotensin II (Ang II) in normal physiology and pathologic states. Losartan is the first nonpeptide orally active Ang II receptor antagonist to reach clinical trials. Losartan was selected for its affinity for Ang II receptors, functional antagonism of Ang II, lack of agonist properties, and oral anti-hypertensive effects. Losartan has been widely used to define the distribution and function of AT receptor subtypes. Although possible roles of the AT2 subtype have been reported, virtually all of the known effects of Ang II are blocked by losartan. Specific AT1 receptor blockade has been broadly compared with ACE inhibition. Possible differences on the basis of AT1 selectivity, bradykinin potentiating effects and Ang II formed by non-ACE pathways are discussed. Losartan blocks the vascular constrictor effect of Ang II, the Ang II-induced aldosterone synthesis and/or release, and the Ang II-induced cardiovascular 'growth' in vitro and in vivo. In various models of experimental hypertension, losartan prevents or reverses the elevated blood pressure and the associated cardiovascular hypertrophy similar to ACE inhibitors. Likewise, in models of renal failure (for example reduced renal mass, puromycin, ochratoxin), losartan, like ACE inhibition, markedly reduced the elevation in blood pressure, proteinuria or sclerosis. In aortocaval shunt, coronary ligation and ventricular pacing models of heart failure, losartan demonstrated a pathological role for Ang II by reversing the associated haemodynamic findings. In SHR-stroke prone, losartan dramatically increased survival while having a limited effect on blood pressure, suggesting a non-pressure dependent effect of Ang II. These collective data show that Ang II exerts complex pathological effects in experimental models of vascular, cardiac, renal and cerebral disease. The effectiveness of losartan in experimental models of heart failure supports its evaluation in clinical trials with patients with heart failure.
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PMID:Discovery of losartan, the first angiotensin II receptor antagonist. 858 79

Knowledge gained from epidemiological studies and clinical trials on hypertension has led to impressive reductions in morbidity and mortality, particularly from stroke and coronary heart disease (CHD) as complications of end-organ damage from untreated, prolonged systemic hypertension. Data on reductions in stroke when hypertension is treated have been clear and convincing from individual clinical trials. Most of these trials, however, have consistently shown only trends towards a reduction in CHD, and few have individually reported statistically significant reductions. A recent meta-analysis, however, suggests that a significant beneficial reduction in CHD exists when the overall data are examined, although at a lower magnitude of benefit and lesser degree of certainty than for stroke. The presence of left ventricular hypertrophy (LVH) increases the risk of subsequent cardiovascular disease events, cardiovascular mortality and all-cause mortality in hypertensive patients. Although echocardiography appears more sensitive than electrocardiography in diagnosing LVH, much of the information demonstrating risks from LVH is from electrocardiography data, and it is not clear how echocardiography will change the risk prediction. Some data from large clinical trials and populations studies suggest that LVH regresses, particularly if the hypertension is adequately treated. A meta-analysis of a large number of small clinical studies in hypertensive patients suggests that the 4 commonly used antihypertensive drug classes, beta-blockers, diuretics, calcium channel antagonists and ACE inhibitors, are all associated with significant reductions in left ventricular mass. While the primary indication for treatment is clearly the hypertension and not the LVH, the presence of the latter necessitates careful treatment and follow-up of these hypertensive individuals.
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PMID:Risk and management of hypertension-related left ventricular hypertrophy. 861 74


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