Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Knowledge of the basic alterations of central hemodynamics in congestive heart failure has failed to explain many aspects of this important syndrome. Increasing attention has recently been paid to compensatory and adaptive mechanisms occurring after the initial insult. Thus, new insights have been gained into the pathophysiology of contraction of hypertrophied myocardium and changes of adrenergic receptors in the myocardium due to chronically increased cardiac sympathetic tone. The role of the renin-angiotensin-aldosterone system in early and advanced congestive heart failure has been further elucidated, and the role of the vasodilating atrial natriuretic peptide is undergoing further definition. New results further clarify the mechanisms leading to breathlessness and muscular fatigue in congestive heart failure, with emphasis shifting from the traditional concept of the importance of increased filling pressures to changes to the peripheral circulation and exercising muscles. Although progress has been made in understanding of the pathophysiology of congestive heart failure, many aspects are still poorly understood and await clarification.
 ...
PMID:Circulatory abnormalities and compensatory mechanisms in heart failure. 204 68

Knowledge of the basic alterations of central hemodynamics in congestive heart failure (CHF) has failed to explain many aspects of this important syndrome. Increasing attention has recently been paid to compensatory and adaptive mechanisms occurring after the initiating insult. Thus, new insights have been gained into the pathophysiology of contraction of hypertrophied myocardium and changes of adrenergic receptors in the myocardium due to chronically increased cardiac sympathetic tone. The role of the renin-angiotensin-aldosterone system in early and advanced CHF has been further elucidated and the role of the vasodilating and natriuretic atrial natriuretic peptide is undergoing further definition. New results further clarify the mechanisms leading to breathlessness and muscular fatigue in chronic CHF with emphasis shifting from the traditional concept of the importance of increased filling pressures to changes to the peripheral circulation and the exercising muscles. Although progress has been made in the understanding of the pathophysiology of CHF, many aspects are still poorly understood and await clarification.
 ...
PMID:Compensatory and adaptive mechanisms in congestive heart failure. 248 Apr 83

We review three new classes of antihypertensive drugs: imidazolines, monatepil, and neutral endopeptidase inhibitors. Imidazolines are a new generation of central acting drugs. Because of their greater affinity for imidazoline receptors rather than alpha 2-adrenoreceptors, they cause less fatigue and dry mouth than the older central acting drugs. Monatepil is a single drug with both calcium antagonist and peripheral alpha 1-antagonist properties. This agent not only lowers blood pressure but also lowers serum cholesterol, an effect mediated by its alpha-antagonism, and has anti-lipid peroxidation properties. Monatepil might become an effective antiatherosclerosis drug. Neutral endopeptidase inhibitors lower blood pressure by inhibiting the metabolism of atrial natriuretic peptide and other vasoactive peptides.
 ...
PMID:Newer antihypertensive drugs. 749 51

The effect of carmoxirole, a presynaptic dopamine (DA2) receptor agonist, on blood pressure, plasma catecholamines, renin-aldosterone and atrial natriuretic peptide and the intracellular concentration and transmembrane fluxes of Na+ and K+, in erythrocytes and platelets was studied in 24 normal men, using a double-blind, parallel study design. After a run-in period of 1 week, the subjects were treated with either placebo (n = 8) or 0.5 mg carmoxirole (n = 16) once daily for 1 week. Blood pressure and heart rate were not changed during carmoxirole administration in these normal men. Surprisingly, no significant effect of carmoxirole was found on the circulating plasma concentration of noradrenaline, adrenaline or dopamine. Other hormones such as renin, aldosterone and atrial natriuretic peptide were also not changed during carmoxirole administration. No significant effect of carmoxirole could be demonstrated on the intracellular concentration of Na+, K+, Mg2+ and Ca2+ and on the transmembrane fluxes of Na+ and K+ in erythrocytes and platelets. In the carmoxirole-treated subjects (n = 16), 6 subjects reported spontaneously adverse events such as syncope, dizziness and vomiting tendencies and/or fatigue.
 ...
PMID:Erythrocyte and platelet cationic concentrations and transport systems in normal volunteers treated with carmoxirole. 790 90

Recent studies of obstructive sleep apnea and its comorbidity with other systemic diseases have stimulated interest in the relationship of apnea to renal disease and hypertension. Polysomnographic sleep studies in patients on dialysis who complain of day-time fatigue or sleepiness reveal significant apnea in up to 73% of those studied. Abnormalities in respiratory controller mechanisms from chronic hypocarbia, metabolic acidosis, and uremic toxins have been blamed for the occurrence of apnea in this setting. Proteinuria and sometimes nephrotic syndrome have been recognized in morbidly obese patients with sleep apnea syndrome. Renal biopsies of such patients have shown glomerulomegaly and focal segmental sclerosis. It is postulated that these lesions may result from increased glomerular filtration and blood flow. Elevated urine output, sodium and chloride excretion, and atrial natriuretic peptide have been well demonstrated in obstructive apnea patients and correct to control levels with treatment of the apnea. Both acute (with each apnea) and chronic daytime blood pressure elevation are frequently observed in sleep apnea patients, and occult sleep apnea is postulated as one possible cause of "primary" hypertension in middle-aged men. In younger patients, such hypertension seems to be more reversible with the elimination of apnea. In older patients, however, the cure of systemic hypertension cannot be guaranteed with the elimination of the apnea, and asymptomatic apnea patients tend not to tolerate the bother and discomfort of apnea treatment with nasal continuous positive airway pressure. Therefore, aside from a careful history regarding sleep symptomatology, polysomnographic studies of clinic populations with primary hypertension to search for apnea as a cause cannot be recommended.
 ...
PMID:Obstructive sleep apnea and the kidney. 830 38

To study effort tolerance in elderly women with different physical activity backgrounds, 52 physically active (PA) and 42 sedentary control women (CO) aged 66-85 yr were assigned to perform cycle ergometer exercise to their volitional maximum. Oxygen uptake, respiratory exchange ratio (RER), heart rate, work power, and rate pressure product were measured to evaluate the severity of exercise. Plasma C-ANP (C-terminus of the atrial natriuretic peptide prohormone) and plasma N-ANP (N-terminus of the atrial natriuretic peptide prohormone) were analyzed as indicators of cardiac load. Eighty-one percent (N = 42) of the PA and 52% (N = 22) of CO performed the ergometer exercise. The mean peak oxygen uptake was 22.6 and 15.1 mL x kg(-1) x min(-1) among PA and CO, respectively. Twenty-two of the 42 PA and 19 of the 22 CO terminated the ergometer exercise before attaining the objective maximum. The most common reasons for termination were the subject's own wish, abnormal cardiovascular response, or lower limb tiredness. Both C-ANP and N-ANP increased after exercise. The increase in plasma C-ANP correlated significantly with a few physiological variables, whereas comparable associations with N-ANP were not found. It is concluded that inexperience of physical exertion and medical as well as physiological factors limit effort tolerance among elderly women. Differences in the response of C-ANP and N-ANP were found that are suggested to be due to differences in the postsecretory mechanisms between these hormones.
 ...
PMID:Effort tolerance in elderly women with different physical activity backgrounds. 947 60

Recent observations have shown that plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) correlate with cardiac function or prognosis in heart failure patients. However, relatively little is known about changes in their plasma concentration during commonly occurring physiological states such as fatigue. Therefore, this study was designed to examine the physiological changes of plasma ANP and BNP concentrations using a chronic sleep-deprivation model. Bicycle ergometer cardiopulmonary exercise tests were performed in 10 healthy volunteers (mean age: 22.7 years). Blood samples for measuring ANP and BNP were drawn during the resting state and immediately after each exercise test. Cardiac output (CO) was measured during the exercise test by the impedance method. The study conditions were designed as follows: (A) a day following a period of normal sleep (control state) and (B) a day preceded by 1 month during which sleep lasted <60% of normal (chronic sleep-deprived state). Results were as follows. (1) Peak oxygen uptake and peak CO decreased during the sleep-deprived state compared with the control state. (2) There was no difference between peak heart rates measured during exercise under the 2 conditions. (3) Plasma ANP concentration during exercise increased significantly during the control state, whereas only a tendency toward increase was observed during the sleep-deprived state. (4) Plasma BNP concentration during exercise tended to increase in the control state compared with the resting state, whereas there was no difference in plasma BNP between after exercise and resting state in the sleep-deprived state. These results indicate that changes of ANP or BNP induced by exercise tended to be decreased by chronic sleep deprivation.
 ...
PMID:Exercise-induced changes in plasma atrial natriuretic peptide and brain natriuretic peptide concentrations in healthy subjects with chronic sleep deprivation. 1040 84

Is heart failure an endocrine disease? Historically, congestive heart failure (CHF) has often been regarded as a mechanical and haemodynamic condition. However, there is now strong evidence that the activation of neuroendocrine systems, like the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system, as well as the activation of natriuretic peptides, endothelin and vasopressin, play key roles in the progression of CHF. In this context, agents targeting neurohormones offer a highly rational approach to CHF management, with ACE inhibitors, aldosterone antagonists and beta-adrenergic blockade improving the prognosis for many patients. Although relevant improvements in clinical status and survival can be achieved with these drug classes, mortality rates for patients with CHF are still very high. Moreover, most patients do not receive these proven life-prolonging drugs, partially due to fear of adverse events, such as hypotension (with ACE inhibitors), gynaecomastia (with spironolactone) and fatigue (with beta-blockers). New agents that combine efficacy with better tolerability are therefore needed. The angiotensin II type 1 (AT(1))-receptor blockers have the potential to fulfil both these requirements, by blocking the deleterious cardiovascular and haemodynamic effects of angiotensin II while offering placebo-like tolerability. As shown with candesartan, AT(1)-receptor blockers also modulate the levels of other neurohormones, including aldosterone and atrial natriuretic peptide (ANP). Combined with its tight, long-lasting binding to AT(1)-receptors, this characteristic gives candesartan the potential for complete blockade of the RAAS-neurohormonal axis, along with the great potential to improve clinical outcomes.
 ...
PMID:Neurohumoral blockade in CHF management. 1196 92