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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

From at least 1928 until about 1940 essential hypertension was reported to be a rare disease among the population in Kenya and Uganda. Currently, it is 1 of the common causes of heart failure and a major cause of cerebrovascular disease in many hospitals in these 2 nations. Field data in these countries suggest that blood pressure rises during adult life, and essential hypertension occurs in salt-sensitive individuals, when sodium chloride daily intake is excessive. If the intake of potassium chloride is less than that of sodium chloride, and the intake of dietary fiber decreases much, as happens when diets are westernized, these may act as subsidiary risk factors. The East African diets are becoming more and more westernized. The 1st major dietary change involves the addition of much salt to low-salt unprocessed foods. With progressive westernization of diets the foods processed by manufacturers replace homegrown staples. These processed foods contain considerably more sodium, rather less potassium, and much less dietary fiber. While this multiple dietary change takes place, blood pressure levels, previously low and not rising with age, begin to rise during adult life. Essential hypertension, once rare, becomes common in sodium sensitive persons. Diets comparable in many respects to the 1930 Kikuyu diet are suggested to reverse essential hypertension. The therapeutic diet should be of low sodium chloride and should contain much unrefined high fiber high starch foods.
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PMID:From normotension to hypertension in Kenyans and Ugandans 1928-1978. 738 2

Combined neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE) inhibition produces greater acute hemodynamic effects than either treatment alone. We investigated whether BMS-182657 (BMS), which bears inhibitory activities against both NEP and ACE, elicited similar enhanced effects. BMS inhibited NEP and ACE, in vitro (IC50 = 6 and 12 nM, respectively) and the pressor response to Ang I in rats. In deoxycorticosterone acetate (DOCA)-salt hypertensive rats sensitive to NEP inhibition but not to ACE inhibition, BMS at 100 mumol/kg i.v. lowered mean arterial pressure (MAP) from 180 +/- 6 to 151 +/- 5 mm Hg. In sodium-depleted, spontaneously hypertensive rats (SHR) sensitive to ACE inhibition but not to NEP inhibition, BMS at 100 mumol/kg p.o. lowered MAP from 151 +/- 4 to 123 +/- 5 mm Hg. Cardiomyopathic hamsters with heart failure were administered vehicle or one of the following (30 mumol/kg i.v.): the ACE inhibitor enalaprilat; the NEP inhibitor SQ-28603; or BMS. Enalaprilat and SQ-28603 had minimal hemodynamic effects. BMS decreased left ventricular end-diastolic pressure by 12 +/- 2 and 10 +/- 1 mm Hg and left ventricular systolic pressure by 27 +/- 2 and 23 +/- 3 mm Hg at 30 and 60 min, respectively (P < .05 vs. each other group). These changes were associated with a 40% increase in cardiac output, a 47% decrease in peripheral vascular resistance and a lowering of MAP by 21 +/- 3 mm Hg at 60 min (P < .05 vs. each other group). There were no significant differences in the changes in heart rate or left ventricular stroke work index among the four groups. Hence, BMS-182657 is a dual inhibitor of NEP and ACE, is antihypertensive irrespective of the activity of the renin-angiotensin system and has acute hemodynamic effects in hamsters with heart failure greater than those produced by selective inhibition of NEP or ACE. The NEP and ACE inhibitory activities of BMS-182657 act synergistically and mimic the interaction resulting from combining selective inhibitors of these enzymes.
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PMID:Cardiovascular effects of the novel dual inhibitor of neutral endopeptidase and angiotensin-converting enzyme BMS-182657 in experimental hypertension and heart failure. 747 62

The aims of treatment of chronic heart failure are to improve the symptoms and the quality of life, reduce mortality and prevent left ventricular dysfunction. Before the first symptom occurs, neurohormonal activation takes place (increased catecholamines and atrial natriuretic peptide levels). Diuretics improve symptoms and are irreplaceable for the elimination of salt and water overload. Loop diuretics are used more often than the thiazides. Their deleterious effects on electrolyte balance are well known. The fact that they activate the renin angiotensin system is a more recent acquisition; the increase in plasma renin activity is a poor prognostic factor. Diuretics potentialize the vasodilator effect of angiotensin converting enzyme inhibitors which inhibit the neurohumoral activation induced by the diuretics. This therapeutic association is very logical, effective and allows reduction in the dosage of the diuretic. To date, there are no large scale controlled studies of the effects of diuretics on mortality. Spironolactone corrects hypokalaemia and hypomagnesaemia induced by loop diuretics. Moreover, it has been shown experimentally in renovascular hypertension and in hyperaldosteronism, that this molecule can prevent myocardial fibrosis, a factor which leads to ventricular dysfunction. The RALES study will analyse the effect of associating spironolactone to diuretic and ACE inhibitor therapy on the mortality of patients in NYHA classes III-IV. The value of digitalis in heart failure patients with sinus rhythm is a classical controversy. Digitalis has a positive inotropic effect (inhibition of NaK-dependent ATPase). More recently, a favourable neurohormonal effect has been reported; digitalis decreases the activation of the sympathetic and renin-angiotensin systems.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Classic treatment of chronic heart insufficiency. What if new?]. 748 8

The history of the treatment of heart failure may be divided into three stages, the consequences of different conceptions of the physiopathology of the disease, with diuretics to counteract salt and water retention, vasodilators to improve conditions of cardiac load, angiotensin converting enzyme inhibitors to limit the effect of neurotumoral and sympathetic activation. There are two main reasons for using calcium antagonist in heart failure, the first being arterial vasodilatation leading to improve systolic function and the second being the beneficial effect on ventricular relaxation. However, their use has been controversial because of the results obtained with the first generation of these drugs. New molecules derived from dihydropyridine have been developed. Clinical trials with these second generation calcium antagonists are analysed.
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PMID:[Calcium antagonists and treatment of chronic heart failure]. 748 13

Epidemiological and clinical studies suggest that low dietary potassium intake may have an important role in determining the development of diseases such as hypertension, and perhaps even stomach cancer, and that increased potassium intake may have beneficial effects in several other conditions. Dietary adjustment or active potassium supplementation has been suggested as a natural, less costly and safe method of increasing potassium levels, although active supplementation with tablets or solutions is not recommended in healthy people with normal serum potassium levels. However, increasing dietary potassium intake in the elderly and in patients with renal impairment must be considered with caution. Diuretics have a long established role in the management of hypertension and heart failure. There is no convincing evidence to suggest that the small reduction in plasma potassium levels associated with low dose thiazide and loop diuretic therapy needs to be routinely prevented by the use of potassium-sparing drugs. In non-digitalised patients little association has been found between mild diuretic-induced hypokalaemia and arrhythmias. Thus, the routine prophylactic use of potassium-sparing diuretics in combination with non-potassium-retaining diuretics for the treatment of hypertension and oedematous states is not justified. Based on current evidence, treating all patients whose serum potassium level decreases below 3 mmol/L is recommended, although for certain patients at particular risk of hypokalaemia, levels may need to be maintained above 3.5 mmol/L. In overt hypokalaemia, several therapeutic options are available to the clinician. These include increased consumption of potassium-rich foods, the use of salt substitutes, medicinal potassium supplementation or distal tubular (potassium-sparing) diuretics.
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PMID:Potassium supplements and potassium-sparing diuretics. A review and guide to appropriate use. 751 Jun 15

The successful introduction of angiotensin converting enzyme (ACE) inhibitors in the treatment of patients with essential hypertension or heart failure has increased interest in the (patho)physiological role of the renin-angiotensin system (RAS). ACE is not only involved in the formation of angiotensin II from angiotensin I, but also inactivates vasoactive substances such as bradykinin and substance P. Accumulation of these substances during treatment with ACE inhibitors may contribute to both their therapeutic action and certain adverse effects associated with their use, such as cough and angioneurotic oedema. Renin inhibitors offer an alternative approach to inhibit the RAS. The major advantage of these, still experimental, drugs is their high specificity for the RAS since angiotensinogen is the only known substrate of renin. The currently available renin inhibitors are pseudopeptides that are rapidly taken up by the liver and excreted in the bile. Consequently, these drugs are subjected to a considerable first pass effect which limits their oral bioavailability. Additionally, plasma elimination half-life times are short and the duration of action is limited. Despite these shortcomings, single oral or intravenous administration results in a 80 to 90% inhibition of plasma renin activity and a slight reduction in blood pressure in patients with hypertension. The extent of blood pressure reduction is dependent on the patient's salt balance. After 1 week of oral treatment with the renin inhibitor remikiren, the antihypertensive effect was reduced in salt-repleted hypertensive patients. Subsequent intravenous administration of the drug did not further affect blood pressure, indicating that it was not the first pass effect that was limiting the efficacy of remikiren.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical pharmacokinetics and efficacy of renin inhibitors. 758 99

At least theoretically, ACE-inhibitors may influence each of the factors involved in the regulation of salt and water metabolism. Angiotensin II exerts an antidiuretic and antinatriuretic action on the kidney through influences on the glomerular filtration coefficient, glomerular filtration rate, mesangial tone, filtration fraction, proximal and distal tubule. Angiotensin II and renin also regulate the input of water and salt through an unequivocal dipsogenic effect. In congestive heart failure angiotensin II participates in the preservation of the glomerular filtration rate through its vasoconstrictor properties on the systemic vessels (maintenance of the perfusion and filtration pressure) as well as on the efferent arteriole (maintenance of the filtration pressure). ACE-inhibition weakens or abolishes these influences. However, two favorable mechanisms may also come into action: rise of cardiac output and improvement in renal blood flow; widening of the filtration surface and increment of the filtration coefficient. The efficacy of these factors depends on renal function, age, functional recovery of the heart, treatment with diuretics, duration of treatment with ACE-inhibitors, duration of action of the ACe-inhibitor used, blockade of the facilitating action on the adrenergic vasoconstriction, formation of vasodilating prostaglandins, reduced degradation of kinins. All these effects may account for the variable and often contradictory clinical results, in particular as concerns the relationship between ACE-inhibition and use of diuretics in congestive heart failure. This also explains the variability of efficacy (from the development of pulmonary edema and requirement of diuretics to diuretic withdrawal and clinical improvement) of the ACE-inhibitors as monotherapy in mild to moderate heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[ACE-inhibitors and water metabolism in heart failure]. 763 56

Left ventricular hypertrophy (LVH) is an early complication of hypertension. To a certain degree, this process counteracts the parietal stress induced by high blood pressure. Genetic factors, obesity, high salt diet and different growth factors, notably angiotensin II and noradrenaline, can also predispose to hypertrophic cardiomyopathy. Left ventricular mass is increased on echocardiography in about 20% of hypertensive subjects. LVH is initially associated with a change in myocardial diastolic function and later with abnormal systolic function. It is a major risk factor, a cause of cardiac failure, reduction in coronary reserve and of ventricular arrhythmias. Treatment of hypertension is associated with regression of LVH and preservation or improvement in myocardial diastolic and systolic functions. The decrease in left ventricular mass could reduce the incidence of cardiovascular complications in hypertension.
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PMID:[Physiopathology of left ventricular hypertrophy]. 764 13

1. Long-term volume homeostasis is linked very closely to long-term arterial pressure control through the renal-body fluid feedback mechanism. A key feature of this control system is the ability of the kidneys to respond to changes in arterial pressure by altering renal excretion of salt and water, often referred to as renal-pressure natriuresis. 2. Quantitative studies indicate that ANP secretion is relatively sensitive to changes in atrial pressure and that the rate of hormonal secretion does not adapt to continuous long-term stimulation. 3. Under normal conditions, the renal-body fluid feedback mechanism for arterial pressure control is very efficient in minimizing changes in body fluid volumes during alterations in sodium intake. Therefore, only small changes in atrial pressure and ANP secretion occur. Alterations in plasma ANP concentration within physiological levels have little effect on renal-pressure natriuresis and, therefore, have little impact on volume homeostasis. 4. When the renal-body fluid feedback mechanism for arterial pressure control is impaired and body fluid volumes are elevated, such as in heart failure, large increases in atrial pressure and ANP secretion occur. The resultant pathophysiological plasma levels of ANP exert sustained natriuretic effects and chronically shift renal-pressure natriuresis to lower arterial pressures. In the absence of this chronic effect of ANP on renal-pressure natriuresis, reduced arterial pressure in compensated heart failure would result in protracted retention of salt and water and additional increments in body fluid volumes.
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PMID:Role of atrial natriuretic peptide in long-term volume homeostasis. 776 35

1. Inhibitors of neutral endopeptidase (NEP) EC 3.4.24.11 were developed to regulate endogenous levels of the natriuretic and vasodilatory hormone atrial natriuretic peptide (ANP). The selective NEP inhibitor SQ 28603 enhanced the increases in plasma ANP and urinary excretion of ANP, cyclic GMP and sodium stimulated by infusion of human ANP in conscious monkeys. SQ 28603 also potentiated the renal and depressor responses to rat brain natriuretic peptide (BNP) in conscious spontaneously hypertensive rats (SHR) and human BNP in conscious monkeys. Therefore, selective NEP inhibitors protected both natriuretic peptides from degradation in vivo and enhanced their biological activities. 2. Selective NEP inhibitors lowered blood pressure in conscious DOCA/salt hypertensive rats and SHR with antihypertensive activity similar to that of exogenous ANP. Furthermore, simultaneous treatment with an angiotensin converting enzyme (ACE) inhibitor enhanced the depressor activity of the NEP inhibitor in SHR. 3. SQ 28603 stimulated urinary excretion of cyclic GMP and sodium in a dose-related manner in conscious dogs with tachycardia-induced heart failure. Addition of the ACE inhibitor captopril significantly reduced blood pressure and systemic vascular resistance while sustaining sodium excretion and increasing cardiac output, glomerular filtration rate and renal blood flow. Therefore, combined NEP and ACE inhibition produced a unique haemodynamic and renal profile in dogs with pacing-induced heart failure. 4. The novel dual metalloprotease inhibitor BMS-182657 potentiated the renal responses to exogenous ANP and suppressed the pressor response to angiotensin I in conscious monkeys, indicating in vivo inhibition of both NEP and ACE.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Potentiation of natriuretic peptides by neutral endopeptidase inhibitors. 776 36


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