UMLS:C0151744 - FACTA Search

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Query: UMLS:C0151744 (myocardial ischemia)
31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelin-1 (ET-1) is overexpressed in the vascular wall in certain models of experimental hypertension: deoxycorticosterone acetate salt-treated rats, deoxycorticosterone acetate salt-treated spontaneously hypertensive rats (SHR), stroke-prone SHR, Dahl salt-sensitive rats, angiotensin II-infused rats, and 1-kidney 1 clip Goldblatt rats; it is not overexpressed in SHR, 2-kidney 1-clip hypertensive rats, or L-NAME-treated rats. In hypertensive rats without generalized vascular overexpression, however, expression of ET-1 was often enhanced in intramyocardial coronary arteries, suggesting a role of endothelin in myocardial ischemia in hypertension. In rats overexpressing ET-1, ET(A/B) and ET(A)-selective receptor antagonists lowered blood pressure and reduced vascular growth, particularly in small arteries, beyond what could be attributed to blood pressure lowering, suggesting a direct effect of ET-1 on growth. Hypertensive rats treated with endothelin antagonists are protected from stroke and renal injury. The ET(A/B) antagonist bosentan induced blood-pressure reductions in mildly hypertensive patients similar to those achieved with an angiotensin-converting enzyme inhibitor. Moderately to severely hypertensive patients presented with enhanced expression of prepro-ET-1 mRNA in the endothelium of subcutaneous resistance arteries, suggesting that these stages of hypertension may respond particularly well to endothelin antagonism. Hypertensive patients with coronary artery disease have increased arterial expression of ET-1, and increased plasma levels of immunoreactive endothelin have been described in black patients. ET-1 plays an important role in atherosclerosis, for which hypertension is an important risk factor. Thus, ET-1 may be involved in experimental and human hypertension. Endothelin antagonists may prove effective as disease-modifying agents if they are shown clinically, as they are experimentally, to offer target organ protection and reduce long-term complications of hypertension. This remains to be demonstrated in humans.
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PMID:State-of-the-Art lecture. Role of endothelin-1 in hypertension. 1052 77

Recent experimental evidence suggests that reactive nitrogen oxide species can contribute significantly to postischemic myocardial injury. The aim of the present study was to evaluate the role of two reactive nitrogen oxide species, nitroxyl (NO(-)) and nitric oxide (NO(.)), in myocardial ischemia and reperfusion injury. Rabbits were subjected to 45 min of regional myocardial ischemia followed by 180 min of reperfusion. Vehicle (0.9% NaCl), 1 micromol/kg S-nitrosoglutathione (GSNO) (an NO(.) donor), or 3 micromol/kg Angeli's salt (AS) (a source of NO(-)) were given i.v. 5 min before reperfusion. Treatment with GSNO markedly attenuated reperfusion injury, as evidenced by improved cardiac function, decreased plasma creatine kinase activity, reduced necrotic size, and decreased myocardial myeloperoxidase activity. In contrast, the administration of AS at a hemodynamically equieffective dose not only failed to attenuate but, rather, aggravated reperfusion injury, indicated by an increased left ventricular end diastolic pressure, myocardial creatine kinase release and necrotic size. Decomposed AS was without effect. Co-administration of AS with ferricyanide, a one-electron oxidant that converts NO(-) to NO(.), completely blocked the injurious effects of AS and exerted significant cardioprotective effects similar to those of GSNO. These results demonstrate that, although NO(.) is protective, NO(-) increases the tissue damage that occurs during ischemia/reperfusion and suggest that formation of nitroxyl may contribute to postischemic myocardial injury.
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PMID:Opposite effects of nitric oxide and nitroxyl on postischemic myocardial injury. 1058 54

There is a need to develop new and more consistent animal models of cardioprotection. Traditionally, outbred dogs, rabbits, and rats have been studied. We determined resistance to ischemia in isolated hearts from inbred strains of rats. Hearts from inbred rats: SS/Mcw (Dahl S, Dahl salt-sensitive), DA/Hsd (Dark Agouti), LEW/Hsd (Lewis), and BN/SsN/Mcw (Brown Norway); and from an outbred rat: Hsd:WIST (Wistar) were subjected to 27 min of global, no-flow ischemia, followed by 3 h of reperfusion. Infarct size in the Brown Norway rat was 2.5 times less than that observed in the Dahl S rat, with the Dark Agouti, Lewis, and Wistar rats intermediate in response. Hearts from Brown Norway rats were also most resistant to ischemia in terms of postischemic enzyme leakage and contractile and vascular function compared with other strains. The average polymorphism rate between strains revealed that such strains were genetically diverse. This study demonstrates strain differences in resistance to myocardial ischemia, suggesting these rats could be used to study a genetic and/or environmental basis for these differences and to provide new animal models for the physiological study of cardioprotection.
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PMID:Resistance to myocardial ischemia in five rat strains: is there a genetic component of cardioprotection? 1074 37

The paper focuses on some aspects of the complex relationship between dietary salt intake and blood pressure. The first part is a short review of the evidence available from epidemiological and clinical studies, indicating that a moderate reduction in dietary salt intake represents an effective non-pharmacological measure for the treatment of hypertension and for the prevention of hypertension-related cardiovascular complications, namely stroke and ischemic heart disease. The second part deals with the role of inherited and acquired factors in the phenotypic expression of the salt-sensitivity of blood pressure. In particular, the influence of sympathetic nervous system hyperactivity, of insulin resistance and of alterations of endothelial function in the pathogenesis of salt-related forms of hypertension are discussed.
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PMID:Increasing evidence for the role of salt and salt-sensitivity in hypertension. 1091 74

The pathogenesis of hypertension in haemodialyzed uraemic patients is multifactorial. The following are involved: sodium and water retention as a result of the impaired excretory capacity of the kidneys, excessively increased activity of the RAAS and sympathetic nerve, increased levels of the vascular constrictor endothelin-1, cumulation of endogenous inhibitors of NO synthesis and reduced formation of vasodepressor factors. As to other factors in the development of hypertension raised intracellular calcium associated with hyperparathyroidism may participate, the stiffness of calcified arteries, erythropoietin treatment and preexisting essential hypertension. Treatment comprises salt restriction below 5 g/day, systematic control of the volume of extracellular fluid by ultrafiltration during every haemodialysis to the level of so-called dry weight and pharmacological treatment in patients where volume control dos not suffice. All drug groups are used. In their selection contraindications are taken into consideration as well as co-morbidity, the dialyzability of antihypertensive drugs and compelling evidence. In patients with a preserved residual diuresis furosemide is administered--125-750 mg/day. Beta-blockers are indicated in patients with IHD, in particular after IM. Calcium blockers are recommended in ventricular hypertrophy and diastolic dysfunction, when beta-blockers are contraindicated and in elderly patients. ACEI indicated in congestive heart failure and left ventricular hypertrophy with systolic dysfunction. Inhibitors of AT1 receptors are an alternative in case of undesirable effects od ACEI. Alpha-blockers and central alpha agonists are used mainly in combinations. In case of failure the haemodialyzation method can be altered or changing the patients to CAPD may be considered. The relationship between BP and the survival of haemodialyzed patients is bimodal. An adverse effect is exerted by a high as well as low BP and in particular by interdialyzation hypotension. The target BP for the haemodialyzed population has not been defined so far. There is, however, evidence that a high BP is independently associated with the de novo development of IHD and MAP above 106 mm Hg with de novo development of cardiac failure. MAP below 98 mm Hg minimalizes the development and progression of left ventricular hypertrophy and MAP below 106 mm Hg the development of heart failure. Long-term survival for 15 and more years is statistically significantly associated with MAP lower than 99 mm Hg.
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PMID:[Hypertension in hemodialyzed uremic patients]. 1095 54

It is mostly acknowledged that 'normal' or 'healthy' ageing of the cardiovascular system is distinct from the increasing incidence and severity of cardiovascular disease with advancing age (e.g. hypertension, ischaemic heart disease and congestive heart failure). It is also recognized that chronological and biological age may differ considerably. Nevertheless, even in the absence of overt coexisting disease, advanced age is always accompanied by a general decline in organ function, and specifically by alterations in structure and function of the heart and vasculature that will ultimately affect cardiovascular performance. Actual biological age is thus the net result of the interaction between age-related and concomitant disease-associated changes in organ function. As cardiovascular performance at a given moment is the net result of interactions between heart rate, intrinsic contractility, diastolic and systolic function, ventricular afterload and coronary perfusion, it is important to be aware of the age-related changes in each of these variables, independent of disease, as they determine cardiac performance at rest and its response to stress in the elderly. The most relevant age-related changes in cardiovascular performance for perioperative management are the stiffened myocardium and vasculature, blunted beta-adrenoceptor responsiveness and impaired autonomic reflex control of heart rate. These changes are of little clinical relevance at rest, but may have considerable consequences during superimposed cardiovascular stress. Such stress can take the form of increased flow demand (as in exercise or postoperatively), demand for acute autonomic reflex control (as in change of posture) or severe disease (as during myocardial ischaemia, tachyarrhythmias or uncontrolled hypertension). It may interfere with diastolic relaxation (i.e. ventricular filling), systolic contraction (i.e. ventricular emptying) and vasomotor control (i.e. arterial pressure homeostasis). Three factors contribute most of the increased perioperative risk related to advanced age. First, physiological ageing is accompanied by a progressive decline in resting organ function. Consequently, the reserve capacity to compensate for impaired organ function, drug metabolism and added physiological demands is increasingly impaired. Functional disability will occur more quickly and take longer to be cured. Second, ageing is associated with progressive manifestation of chronic disease which further limits baseline function and accelerates loss of functional reserve in the affected organ. Some of the age-related decline in organ function (e.g. impaired pulmonary gas exchange, diminished renal capacity to conserve and eliminate water and salt, or disturbed thermoregulation) will increase cardiovascular risk. The unpredictable interaction between age-related and disease-associated changes in organ functions, and the altered neurohumoral response to various forms of stress in the elderly may result in a rather atypical clinical presentation of a disease. This may, in turn, delay the correct diagnosis and appropriate treatment and, ultimately, worsen outcome. Third, related to the increased intake of medications and altered pharmacokinetics and pharmacodynamics, the incidence of untoward reactions to medications, anaesthetic agents, and medical and surgical interventions increases with advancing age. On the basis of various clinical studies and observations, it must be concluded that advanced age is an independent predictor of adverse perioperative cardiac outcome. It is to be expected that the aged cardiovascular risk patient carries an even higher perioperative cardiac risk than the younger cardiovascular risk patient. Although knowledge of the physiology of ageing should help reduce age-related complications, successful prophylaxis is hindered by the heterogeneity of age-related changes, unpredictable physiological and pharmacological interactions and diagnostic difficultie
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PMID:The aged cardiovascular risk patient. 1157 7

Underlying causes and precipitating causes of congestive heart failure (CHF) should be treated when possible. Older persons with CHF and normal left ventricular (LV) ejection fraction should have maintenance of sinus rhythm, treatment of hypertension and myocardial ischemia, slowing of the ventricular rate below 90 beats/minute, and reduction of salt overload. First-line drug treatment in the management of these persons is the use of loop diuretics combined with beta blockers as tolerated. Angiotensin-converting enzyme (ACE) inhibitors should be administered if CHF persists despite diuretics and beta blockers. If persons are unable to tolerate ACE inhibitors because of cough, rash, or altered taste sensation, angiotensin II type 1 receptor antagonists should be given. If CHF persists despite diuretics, beta blockers, and ACE inhibitors or the person is unable to tolerate beta blockers, ACE inhibitors, and angiotensin II type 1 receptor antagonists, isosorbide dinitrate plus hydralazine should be administered. Calcium channel blockers should be used if CHF persists despite administration of diuretics and the person is unable to tolerate beta blockers, ACE inhibitors, angiotensin II type 1 receptor antagonists, and isosorbide dinitrate plus hydralazine. Digoxin, beta blockers, verapamil, and diltiazem may be used to slow a rapid ventricular rate in persons with supraventricular tachyarrhythmias. Digoxin should not be used in persons with CHF in sinus rhythm with normal LV ejection fraction.
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PMID:Left ventricular diastolic heart failure with normal left ventricular systolic function in older persons. 1157 22

Endothelin-1 (ET-1) is a powerful vasoconstrictor peptide and regulator of blood flow that plays an important role in blood pressure (BP) elevation in some models of experimental hypertension such as DOCA-salt rat, DOCA-salt-treated spontaneously hypertensive rats (SHR), stroke-prone SHR, Dahl salt-sensitive rats, angiotensin II-infused rats, and one-kidney, one-clip Goldblatt rats, but not in SHR, two-kidney, one-clip hypertensive rats, transgenic (mREN2)27 rats, or Nomega-nitro-L-arginine methyl ester chronically treated rats. In those models of hypertension in which ET-1 plays a vasoconstrictor role, ET-1 was shown to be overexpressed in the vessel walls, or BP has been lowered by administration of ET(A/B)- and ET(A)-selective receptor antagonists. In these experimental models, endothelin receptor antagonists also regressed vascular growth and inflammation, and improved endothelial dysfunction. Hypertensive rats treated with endothelin antagonists were protected from stroke and renal injury. In hypertensive rats without generalized vascular overproduction of ET-1, expression of ET-1 was often enhanced in intramyocardial coronary arteries, suggesting a role of ET in myocardial ischemia in hypertension. Moderate-to-severe hypertensive patients presented enhanced expression of pre-proET-1 mRNA in the endothelium of subcutaneous resistance arteries, suggesting that this stage of hypertension may respond particularly well to endothelin antagonism. In some hypertensive patients, exaggerated vascular responses to ET-1 were found. Hypertensive patients with coronary artery disease have increased arterial expression of ET-1. Increased plasma levels of immunoreactive ET have been described in African Americans. ET-1 plays an important role in atherosclerosis, for which hypertension is an important risk factor, and in ischemic heart disease and stroke. Endothelin-1 may also be involved in other forms of vascular disease, including pulmonary hypertension, after angioplasty restenosis, after allograft vasculopathy, and vasculitis. Thus, ET-1 may participate in vascular damage in cardiovascular disease and in BP elevation in experimental models and in human hypertension. Endothelin antagonists could become effective disease-modifying agents in different forms of cardiovascular disease.
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PMID:Role of endothelin-1 in hypertension and vascular disease. 1141 70

Minoxidil is a direct vasodilator that has been in use for over two decades. It is used primarily to reduce blood pressure in hypertensives who have been poorly controlled on various multidrug regimens. Although minoxidil is extremely effective, its usefulness is limited by its tendency to increase the pulse rate and to trigger salt and water retention. The latter may be incapacitating in some patients. Therefore, minoxidil is typically administered with both a diuretic and an agent that can control the pulse rate, such as a beta blocker. Minoxidil has several other side effects that may limit its use, including hypertrichosis, aggravation of myocardial ischemia and/or left ventricular hypertrophy, and (infrequently) pericardial effusions. If a patient's hypertensive pattern is sufficiently severe to warrant contemplation of minoxidil therapy, referring the patient to a hypertension specialist should be strongly considered. (c) 2001 by LeJacq Communications, Inc.
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PMID:Direct vasodilators and their role in hypertension management: minoxidil. 1141 93

A comparison of the cardiovascular actions of the extract of Radix Stephaniae Tetrandrae (RST), the root of a Chinese hero Stephania tetrandra S Moore, in rats with those of tetrandrine (Tet), the best known active component of RST was reviewed. The RST extract inhibits Ca2+ influx into the myocyte and reduces protein release during reperfusion with a Ca2+ containing solution following perfusion with a Ca2+ free solution (Ca2+ paradox), and arrhythmia during reperfusion in the isolated perfused heart. It also reduces the infarct size induced by ischemia/reperfusion in vitro and in vivo. In addition, the RST extract suppresses elevation of arterial blood pressure in DOCA-salt hypertensive rats. It does not further reduce the heart rate and coronary flow significantly during myocardial ischemia. The effects are similar to those of Tet. When compared with the same doses of Tet alone, the RST extract, of which 9% is Tet, produces equally potent effects on infarction, arrhythmias, coronary flow and heart rate, and has a greater inhibitory effect on protein release during Ca2+ paradox. The combination at 1:1 ratio of Tet and fangchinoline (Fan), another main component, which constitutes 6% of the RST extract and has no significant effects on the heart, produces comparable effects on protein release during Ca2+ paradox as Tet alone. The observations suggest that the efficacy of the RST extract cannot be accounted for by Tet alone. Some of the effects may be due to an interaction between the components of the extract. The RST extract also produces similar effects as verapamil, a prototype Ca2+ channel antagonist widely used in the treatment of ischemic heart diseases and hypertension, except that verapamil, at 1 mumol/L, a concentration that produces similar cardiac effects as the RST extract, further reduces heart rate significantly during ischemia. So the RST extract may be a therapeutically better agent in the treatment of ischemic heart diseases and hypertension than Ca2+ channel antagonists because of the absence of the inhibitory effect on heart rate during myocardial ischemia.
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PMID:Cardiovascular actions of Radix Stephaniae Tetrandrae: a comparison with its main component, tetrandrine. 1160 80

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