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

Isolated calcium-tolerant rat ventricular cardiomyocytes were used to characterize the effects of atrial natriuretic peptide (ANP), Angiotensin II (AII) and their interaction on the myocardial contraction-/relaxation pattern free of interference from other types of cardiac cells. Binding of 125I-ANP showed a KD of 12 pM and approximately 600 binding sites per cell. At 37 degrees C (rate 140 bpm) ANP decreased the contraction maximum with an EC50 of about 70 pM, maximal decrease was 35%. ANP (10(-7) M) raised cellular cyclic-GMP from 0.76+/-0.12 to 1.32+/-0.13 pmole/10(6) cells (73%, p less than 0.05). Angiotensin II increased contractility by a maximum of 32% at 10(-7) M; the EC50 was 8 x 10(-10) M. AII markedly delayed relaxation (reduction of maximum relaxation velocity from 0.092 to 0.063 mm/s; p less than 0.05). ANP (10(-7) M) increased the effect of AII (10(-8) M) on contractility by 66% without changing relaxation parameters significantly. This unexpected interaction may be relevant in pathological conditions where both AII and ANP are stimulated, such as heart failure or secondary hypertension.
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PMID:Action of atrial natriuretic peptide and angiotensin II on the myocardium: studies in isolated rat ventricular cardiomyocytes. 255 Dec 88

Angiotensin II can stimulate the sympathetic system and inhibit vagal (parasympathetic) outflow under experimental circumstances in animals. Blockade of angiotensin II formation by angiotensin-converting enzyme (ACE) inhibitors might therefore be expected to result in a reduction of sympathetic activity and enhanced parasympathetic activity. Whether this is so in normotensive or hypertensive humans and in human cardiac failure is unclear, since available techniques for recording activity of the sympathetic and parasympathetic systems are imperfect. Nevertheless, most evidence that comes from measurements of venous norepinephrine suggests that the ACE inhibitors have little or no effect on sympathetic activity in normotension and hypertension, although the activated sympathetic system in severe cardiac failure is probably suppressed. It appears that the ACE inhibitors have a parasympathomimetic action that may contribute to the hemodynamic effects of these drugs. Additional information using direct recordings of sympathetic traffic or measurements of norepinephrine "spillover" is needed to clarify the effects of ACE inhibitors on the sympathetic system.
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PMID:Sympathetic nervous system during converting enzyme inhibition. 257 49

1. Angiotensin II (AII) acts as a potent pressor agent directly, by virtue of its vasoconstrictor activity and indirectly, by the volume expansion resulting from stimulation of aldosterone release from the adrenal cortex, leading to sodium and water retention. Various approaches of interfering with the enzymatic cascade leading to the production of AII have been made in an attempt to define therapeutic agents for the control of hypertension and heart failure. 2. AII receptor antagonists, to date, lack oral activity and have a relatively short duration of action, limiting their clinical usefulness. Inhibitors of angiotensin converting enzyme block AII production, are orally active and have been used successfully in the control of hypertension and in the treatment of congestive heart failure. 3. An ideal approach to the blockade of the renin-angiotensin system (RAS) is the inhibition of renin, an enzyme with only one known substrate (angiotensinogen) which catalyzes the first and rate-limiting step in the RAS. Early attempts to discover a renin inhibitor focused on immunologic inhibitors of renin, fragments of the prorenin sequence and compounds related to pepstatin, a potent pentapeptide inhibitor of pepsin and less potent inhibitor of renin. None of these approaches proved feasible for a variety of reasons including poor absorption, short duration of action and weak activity. 4. Substrate analogs offer the greatest promise for clinically useful renin inhibitors. Most recently, synthesis of compounds mimicking the enzyme transition state, the condition of greatest binding affinity, has resulted in renin inhibitors with potencies in the nanomolar range, which have shown hypotensive activity. These compounds contain at least one peptide bond and have limited oral activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renin inhibitors: specific modulators of the renin-angiotensin system. 265 8

Angiotensin converting enzyme (ACE) inhibitors are the only therapeutic agents used in the treatment of chronic heart failure that have been shown to both improve symptoms and prolong life. These agents produce long-term haemodynamic and clinical benefits in about 60-65% of patients. The only reliable means of determining which patients are most likely to respond favourably to treatment is by a therapeutic trial; the response cannot be predicted by demographic factors, pretreatment left ventricular function or plasma renin activity. In addition to their symptomatic benefits, ACE inhibitors reduce the mortality of patients with chronic heart failure, possibly by decreasing ventricular wall stress and decreasing the frequency and complexity of ventricular arrhythmias. The most serious adverse effects of treatment, hypotension, functional renal insufficiency and potassium retention, occur most commonly in patients with the most advanced disease [New York Heart Association (NYHA) class III and IV heart failure] and when efforts are made to block the formation of angiotensin (Ang) II continuously (as with the use of long-acting ACE inhibitors). The unique characteristics of the ACE inhibitors support their use as first-line agents in patients with chronic heart failure.
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PMID:The current status of angiotensin converting enzyme inhibitors in the management of patients with chronic heart failure. 268 5

1. The identification of a vascular wall renin angiotensin system and of angiotensin converting enzyme on the luminal surface of the endothelium in many tissues, including the brain, has stimulated research on the influence of the renin angiotensin system on regional blood flows. 2. In experimental studies inhibition of the angiotensin converting enzyme shifts the limits of cerebral blood flow autoregulation towards lower blood pressure values. 3. In patients with chronic arterial hypertension and in patients with chronic heart failure cerebral blood flow is not changed by acute or chronic angiotensin converting enzyme inhibition, despite in some cases pronounced reductions in the mean arterial blood pressure. Angiotensin converting enzyme inhibition does not change ischaemic regional cerebral blood flow in acute stroke. 4. It is concluded that following angiotensin converting inhibition cerebral blood flow is maintained at an unchanged level. The mechanism may include inhibition of locally produced angiotensin II leading to a selective dilation of larger cerebral arteries with a compensatory constriction of the smaller cerebral arteries.
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PMID:Angiotensin converting enzyme inhibition and cerebral circulation--a review. 269 Sep 8

Captopril alone as therapy for mild heart failure was compared with a combination of frusemide and amiloride in a double-blind randomised crossover trial in 14 patients who had previously been treated with diuretics. Although 10 patients remained stable on captopril alone, 4 patients deteriorated, with the development of pulmonary oedema of breathlessness. All 4 patients had had pulmonary oedema previously, unlike the patients who remained stable. Angiotensin converting enzyme inhibition alone is not sufficient treatment for patients with mild heart failure and a history of overt pulmonary oedema.
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PMID:Double-blind comparison of captopril alone against frusemide plus amiloride in mild heart failure. 288 42

Withdrawal of captopril therapy for cardiac failure results in increments in plasma cortisol, noradrenaline and heart rate. To determine whether these changes related to the concomitant rise in circulating angiotensin II, we infused angiotensin II at 0.5, 2, 4 and 8 ng/kg/minute, each infusion lasting for 1 hour, in 4 patients during maintenance captopril therapy for heart failure. A control solution of 5% dextrose was infused over a similar time interval on a separate day. The study was performed under metabolic balance conditions, with constant body posture and continuous haemodynamic monitoring. Angiotensin II induced the expected rise in arterial pressure and in plasma aldosterone. In contrast the diurnal decline in plasma ACTH and cortisol was not altered, and no changes in noradrenaline or heart rate were observed. Plasma angiotensin II appears to have little or no effect on ACTH, cortisol, noradrenaline and heart rate under the conditions of this study.
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PMID:Hormone and haemodynamic effects of angiotensin II infusion during captopril treatment for heart failure. 298 94

Angiotensin converting enzyme (ACE) inhibitors are not known to have a direct effect on the myocardium. However, there is some evidence to suggest that they can play an important role in protecting the heart during the evolution of hypertensive and coronary arterial disease, both acutely and on a long term basis. Reduction of afterload by balanced arterial and venular dilatation has led to a sustained improvement of cardiac performance both in hypertension and heart failure. Reversal of cardiac hypertrophy has been shown to restore inotropic responsiveness to stimulators of the adenylate cyclase system. Following myocardial infarction, captopril has prevented undue ventricular dilatation and normalized left ventricular chamber stiffness; this prevented deterioration of cardiac function and improved long term survival after infarction. Control of secondary aldosteronism and prevention of hypokalaemia can play an important role in the prevention of cardiac arrhythmias. The lack of reflex sympathetic stimulation during long term captopril therapy can also play a favourable role in that respect. Although highly speculative, evidence is accumulating that ACE inhibition could have a cardioprotective effect in acute myocardial ischaemia. It is based on the demonstration that renin can be produced by myocardial cells, that angiotensin is liberated by the ischemic myocardium and that angiotensin in high renin conditions plays an active constrictor role in regulating the coronary circulation.
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PMID:Prospectives for angiotensin converting enzyme inhibition in heart diseases. 300 6

The renin-angiotensin system appears to have evolved millions of years ago as a primary attempt to preserve circulatory homeostasis at a time when the principal cause of a low cardiac output was intravascular volume depletion. Angiotensin II supported systemic BP by direct systemic vasoconstriction, by facilitating the central and peripheral effects of the sympathetic nervous system, by promoting renal sodium retention by the production of aldosterone, and by increasing total body water by enhancing thirst and the synthesis of vasopressin. In addition, angiotensin II evolved as an important mechanism to preserve the glomerular filtration rate in low-flow states. These actions of angiotensin II were beneficial when the system first evolved, but its activation in patients with heart failure not only fails to reverse the low-output state but further exacerbates loading conditions in the left ventricle, thereby leading to worsening heart failure. Moreover, increased levels of angiotensin II cause heightened sympathetic nervous activity, potassium depletion, and hyponatremia, each of which can lead to further clinical deterioration. Therefore, activation of the renin-angiotensin system in heart failure might appear (at first) to be a maladaptive response. Recent evidence, however, suggests that this hormonal system continues (even in heart failure) to carry out the primary functions for which it was designed. Angiotensin II plays an important role in preserving systemic BP and in preserving the glomerular filtration rate as renal artery pressure and renal blood flow decline; in addition, by stimulating the synthesis of aldosterone, the renin-angiotensin system provides an important role for potassium disposal.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adaptive and maladaptive actions of angiotensin II in patients with severe congestive heart failure. 303 91

The renin-angiotensin system is activated in heart failure in proportion to the severity of the haemodynamic derangement and to diuretic dose. Angiotensin converting enzyme (ACE) inhibitors reduce circulating levels of angiotensin II and aldosterone and, in some patients, plasma noradrenaline, vasopressin and cortisol. Typically there is potassium retention and a minor increase in plasma potassium, but cumulative sodium balance may increase or decrease depending on pretreatment fluid and haemodynamic status and on policy regarding diuretic dose. Circulatory dynamics usually improve and blood flow to the brain, myocardium and kidneys is preserved. Changes in glomerular filtration rate are dictated by haemodynamic characteristics and, again, by diuretic dose and dietary sodium. There are potential hazards with ACE inhibitor therapy but most problems can be anticipated and avoided. Future trends may include the introduction of ACE inhibitors with or without concomitant diuretic therapy in early cardiac failure, and intravenous ACE inhibition immediately after acute myocardial infartion. Whether the ACE inhibitors will prove more successful than alternative antihypertensive agents in preventing cardiac complications (including heart failure) of hypertension, is an intriguing question.
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PMID:Converting enzyme inhibitors in heart failure. 304 97


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