Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Electrolyte abnormalities are a frequent and potentially hazardous complication in patients with heart failure. This may be due to the pathophysiological alterations seen in the heart failure state leading to neurohumoral activation (stimulation of the renin-angiotensin-aldosterone system, sympathoadrenergic stimulation), and due to the complications of therapy with diuretics, cardiac glycosides or ACE inhibitors. Patients with heart failure may exhibit hyponatremia due to a decrease in water excretion, which may be related to the enhanced release of both angiotensin and vasopressin and can be exaggerated by diuretic therapy. Along with potassium and calcium, magnesium influences cardiovascular function. Magnesium and potassium deficiencies play an important role in the development of cardiac arrhythmias. Magnesium is essential for the maintenance of intracellular potassium concentration. Although there are conflicting data regarding the prevalence of hypomagnesemia in patients with chronic heart failure (the values range from 7-37%), multiple studies have documented lower magnesium concentrations in patients with heart failure than in normal controls. As magnesium and potassium are mainly intracellular ions, measurements in serum or plasma are of limited value to assess magnesium status. There was no correlation between the intracellular electrolyte content and the electrolyte levels in plasma, either for mononuclear cells or erythrocytes or for myocardial and skeletal muscle. Loop diuretics (e.g. furosemide) are supposed to cause a substantial loss of both magnesium and potassium in the plasma and intracellular space. The potassium-sparing diuretics amiloride and triamterene are reported to also exert magnesium-sparing effects. Recently, ACE inhibitors have been documented to have important magnesium-conserving actions, possibly via their effect on glomerular filtration. Hyperkalemia, secondary to the use of ACE inhibitors in patients with heart failure, is well documented. Digoxin directly limits the renal tubular reabsorption of magnesium, therefore increasing magnesium excretion. Low magnesium and potassium concentrations increase cardiac glycoside toxicity. In contrast, elevated levels of magnesium decrease the sensitivity of human myocardium to antiarrhythmogenic actions of cardiac glycosides, without affecting maximally developed tension. Moreover, magnesium increases binding affinity of cardiac glycosides to the receptor. The antiarrhythmic action of magnesium is suspected to be mediated by a reduced sensitivity to electrophysiological changes induced by Ca2+, thus indicating Ca2+ antagonistic properties of magnesium. Magnesium deficiency has also been implicated in sudden death, notably in patients with congestive heart failure. Therefore, when treating congestive heart failure, one must consider how to prevent depletion of electrolytes or how to replete potassium and magnesium in deficiency states.
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PMID:Heart failure and electrolyte disturbances. 150 35

Urinary digoxin-like factor, ADH, sodium and potassium excretion and urine osmolality were studied during the development of two pathogenically different models of hypertension, DOCA-salt (low-renin) and Gold-blatt 2 kidney-1 clip (renin-dependent). Urinary digoxin-like factor was increased in rats that were given saline (NaCl 1%) to drink, uninephrectomized-salt and DOCA-salt rats, with no significant differences between the two groups urinary ADH was elevated in DOCA-salt rats during the study, compared with uninephrectomized-salt rats. Urinary digoxin-like factor and urinary ADH were not significantly modified in Goldblatt 2 kidney-1 clip and sham-operated rats. In addition, positive correlations between digoxin-like factor urinary excretion and urinary ADH and also with sodium urinary excretion were found. These data suggest that: a) digoxin-like factor and ADH could play a role in the pathogenesis of DOCA-salt but not in Goldblatt 2 kidney-1 clip hypertension. b) A common mechanism may stimulate ADH and digoxin-like factor simultaneously. c) Digoxin-like factor plays a role in the control of urinary sodium excretion.
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PMID:Urinary excretion of digoxin-like factor (DLF) and ADH during DOCA-salt and Goldblatt 2 kidney-1 clip hypertension development. 219 65

We performed an epidemiological study on the atrial natriuretic factor pattern in a young population. Subjects were recruited in the Ospedale Militare Principale of Rome among young men liable to conscription, whose hospitalization was due either to essential hypertension or to other pathologies (not influencing our study, such as headache etc.). The recruitment lead to the formation of three different groups: normotensives, normotensives with family history of hypertension (mother and/or father) and hypertensives. On the morning of the study (after 7 days of pharmacological wash-out, under a diet containing 120 mEq of Na+/die), blood samples were taken. Plasma atrial natriuretic factor, renin activity and aldosterone were assayed by RIA. Digoxin-like immunoreactive substance was assayed by a solid-phase radioimmunoassay, following the extraction of plasma. Serum creatinine, sodium, potassium and urinary sodium and potassium (24 h before the study) were assayed by standard methods. Urinary kallikrein was assayed by chromogenic substrate S-2266. So far, we have studied 60 subjects (26 hypertensives, 21 normotensives and 13 normotensives with family history) and we wish to discuss in this article the preliminary results concerning the atrial natriuretic factor and its relationship with renin activity, aldosterone and blood pressure. Our results show that the mean plasma levels of atrial natriuretic factor in the hypertensive group were higher, although not significantly, than those of the other two groups and that the normotensives with family history had slightly higher levels as compared to normotensives (Delta % = + 7.4).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Atrial natriuretic factor: an epidemiological study. Preliminary results]. 252 19

The effects of intravenous captopril and intravenous digoxin given separately and in combination on rest and exercise hemodynamics were studied in 16 patients with severe heart failure and sinus rhythm. When given separately, both captopril and digoxin decreased the pulmonary capillary wedge pressure by, respectively, 24% (p = 0.003) and 34% (p = 0.004) and systemic vascular resistance by 23% (p = 0.09) and 20% (p = 0.03). Only digoxin increased cardiac index by 23% (p = 0.03) and stroke work index by 52% (p = 0.01). During maximal exercise, captopril alone decreased systemic vascular resistance by 28% (p = 0.0002) and increased cardiac index by 33% (p = 0.02). Digoxin alone decreased pulmonary capillary wedge pressure by 11% (p = 0.04) and increased stroke work index by 44% (p = 0.01). The combination of captopril and digoxin resulted in a decrease in pulmonary capillary wedge pressure and systemic vascular resistance and an increase in cardiac index and stroke work index both at rest and during exercise that was greater than values observed with either drug given alone. Cardiac index response to the combination of captopril and digoxin correlated with baseline serum aldosterone concentration (r = 0.81, p less than 0.001) and plasma renin activity (r = 0.74, p less than 0.0002). A significant decrease in norepinephrine concentration was noted after digoxin was administered alone or added to captopril. These findings demonstrate that in patients with severe heart failure, the acute administration of captopril and digoxin has an independent salutary hemodynamic effect. The combination of these agents, however, has an adjunctive effect on cardiac function at rest and during exercise.
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PMID:Comparative hemodynamic and neurohormonal effects of intravenous captopril and digoxin and their combinations in patients with severe heart failure. 256 44

We measured five hormones presumably involved in fetal homeostasis in specimens obtained by cordocentesis for clinical indications from 106 fetuses. Norms for atrial natriuretic factor, digoxin-like immunoreactive substance, plasma renin activity, norepinephrine, and epinephrine were derived from fetuses ultimately shown to be free of detectable abnormality. Atrial natriuretic factor, digoxin-like immunoreactive substance, and plasma renin activity were unrelated to umbilical vessel source or gestational age. Digoxin-like immunoreactive substance was directly related to PCO2 (r = 0.63, p = 0.02). Digoxin-like immunoreactive substance level was elevated in all fetal disease states studied except isoimmunization. The level of atrial natriuretic factor was elevated in fetuses with immune hydrops (NS). Norepinephrine and epinephrine levels were higher in the umbilical artery than in the vein (p = 0.05 and 0.006, respectively). There was a significant correlation between norepinephrine and gestational age in normal fetuses (r = 0.7637, p less than 0.025) and between both catecholamines and many of the respiratory blood gas measurements, with pH and PCO2 being the major determinants. Most disease states were associated with an elevated norepinephrine concentration. There was a negative correlation between plasma renin activity and base deficit (p less than 0.0001). Plasma renin activity was elevated in fetuses with idiopathic growth retardation and nonimmune hydrops (p less than 0.05 for each). In summary, fetal homeostasis as reflected by these five hormones was altered by a variety of disorders. With these baseline values the effects of direct or indirect fetal therapy can begin to be studied.
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PMID:Atrial natriuretic factor, digoxin-like immunoreactive substance, norepinephrine, epinephrine, and plasma renin activity in human fetuses and their alteration by fetal disease. 297 84

Abnormalities in sodium metabolism, including the presence of endogenous circulating digitalis-like sodium transport inhibitors, have been implicated in the genesis of essential hypertension. Digitalis has also been reported to affect adrenal steroid output in vitro. We studied the effects of 4 days of treatment with the digitalis glycoside digoxin upon blood pressure, the renin-aldosterone axis, and pressor and steroidogenic responses to graded norepinephrine, angiotensin, and ACTH infusions in six normal men after pretreatment with dexamethasone. Digoxin produced no significant changes in blood pressure, urinary electrolyte or aldosterone excretions, PRA or aldosterone concentrations, or the incremental responses of aldosterone or cortisol to angiotensin or ACTH. However, digoxin significantly augmented pressor responsiveness to both norepinephrine and angiotensin without significantly affecting the steady state baroreceptor-heart rate reflex. These findings support the hypothesis that digitalis-like factors may have important effects upon arterial blood pressure control in man.
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PMID:Effects of digoxin on responsiveness to the pressor actions of angiotensin and norepinephrine in man. 631 64

Contractile properties and micromorphology of the human myocardium were studied in bioptates of the right auricula at the heart failure and its pharmacological correction. It is shown that the chronoinotropic dependence of trabecular muscles of the human heart is a negative one. Vegetation of the connective tissue in the myocardium begins at the stage of development of its hypertrophy. Digoxin in combination with diuretics improves contractile properties and decreases expressiveness of dystrophic changes in myocardiocytes. Combination of the mentioned means with a blocker of the renin-angiotensin system, kapothenum in particular, not only improves the state of the contractile apparatus of the heart, but also causes a reverse development of the hyperplasive connective tissue.
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PMID:[Morphological and functional characteristics of myocardium in patients with cardiac insufficiency and its pharmacologic correction]. 775 7

The incidence and prevalence of heart failure is on the rise. It has become the single most expensive health care item in the United States and the number one discharge diagnosis in the elderly. The goals of therapy include both prevention and treatment of heart failure. In recent years research studies and randomized clinical trials have revolutionized the understanding of the pathophysiology and treatment of this disease. This article focuses on the medical management of chronic systolic heart failure based on the pathophysiology of the disease. Systolic heart failure is characterized by a decrease in left ventricular function and cardiac output, which results in activation of several neurohormonal compensatory systems. The long term effects of this neurohormonal activation leads to further deterioration of cardiac function. The use of hydralazine and nitrates to reduce the systemic vascular resistance was the first to show an improvement in mortality and morbidity. Then angiotensin converting enzyme inhibitors, by inhibiting the renin angiotensin system, demonstrated a greater improvement in mortality and morbidity. More recently the inhibition of the sympathetic stimulation with beta-blockers has been shown to have an additive effect on morbidity and mortality in combination with angiotensin-converting enzyme inhibitors. Digoxin and diuretics remain important for improving symptoms and decreasing hospitalizations but have not been shown to decrease mortality. The most recent advance in the treatment of cardiac failure is the demonstration that the aldosterone antagonists, spironolactone decreases morbidity and mortality.
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PMID:Therapy of heart failure. 1076 77

Large-scale clinical trials of vasodilators with nitrates and hydralazine and with angiotensin-converting enzyme (ACE) inhibitors in the 1980s and early 1990s provided the first credible evidence that medical therapy can prolong survival in patients with chronic heart failure (CHF). Moreover, patients treated with ACE inhibitors required fewer hospitalizations for worsening heart failure (HF). Nonetheless, the prognosis in patients with HF remains bleak, and better therapies are urgently needed. Recently, beta-blockers and spironolactone have been shown to reduce mortality when added to ACE inhibitors, diuretics, and digoxin. Digoxin has a neutral effect on overall mortality but does reduce the rate of hospitalization. Angiotensin II receptor blockers (ARB) inhibit the AT1 angiotensin receptor, which mediates the deleterious effects of the renin-angiotensin system, and may provide advantages over ACE inhibitors or advantages when used in combination with ACE inhibitors. Newer drugs that interfere with other mechanisms that contribute to progression of heart failure are also under study. As new therapies prove effective in large populations, they lead to a mandate for polypharmacy. The long-term solution to this clinical problem is to develop sensitive and reliable markers that can predict response in individual patients or monitor effectiveness of therapy.
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PMID:Heart failure: future treatment approaches. 1083 Jul 93

Most patients with heart failure today are treated by primary care practitioners, not cardiologists. The Consensus Recommendations for the Management of Chronic Heart Failure, developed by the Advisory Council to Improve Outcomes Nationwide in Heart Failure, provide practice guidelines for the prevention, diagnosis, and treatment of heart failure. Although hemodynamic abnormalities contribute to the symptoms of heart failure, disease progression is attributable to neurohormonal abnormalities, primarily activation of the renin-angiotensin system and the sympathetic nervous system. Pharmacologic treatment that antagonizes these neurohormonal abnormalities reduces the morbidity and mortality associated with heart failure. Guidelines recommend that patients with systolic dysfunction and symptoms of fluid retention receive a diuretic followed by an angiotensin-converting enzyme inhibitor, and, once the patient is euvolemic, a beta-blocker. Digoxin may be added to therapy for patients with persistent symptoms or rapid atrial fibrillation. Clinical trials have shown that such combination regimens reduce the risk of hospitalization and death in patients with heart failure.
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PMID:New strategies for improving heart failure management: a primary care perspective. 1123 30


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