Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelins (ET) are a family of peptides with potent biological properties. Endothelial cells produce exclusively ET-1 while other tissues produce ET-2 and ET-3. The production of ET requires an increase in intracellular Ca2+. This increase can be induced by physical chemicals (i.e. hypoxia) or receptor-operated stimuli (i.e. thrombin, angiotensin II, arginine vasopressin, transforming growth factor beta 1, interleukin-1). Most of ET is released abluminally towards vascular smooth muscle and less luminally. The main vascular effect of ET are vasodilation (transient), profound and sustained vasoconstriction as well as proliferation of vascular smooth muscle. These biological effects are mediated by distinct receptors. Three ET receptors have been cloned, i.e. ETA-, ETB- and ETC-receptors. In vascular tissue ETA-receptors are expressed on vascular smooth muscle and responsible for vasoconstriction. ETB-receptors are expressed on endothelium and linked to nitric oxide and/or prostacyclin release. Activation of these receptors explains the transient vasodilation with intraluminal application of ET. Vascular smooth muscle cells can express ETB-receptors which contribute to ET-induced vasoconstriction particularly at lower concentrations. The role of the recently cloned ETC-receptor in the vasculature is still uncertain. ET production is increased (as judged from circulating plasma levels) in vascular disease and atherosclerosis in particular, in myocardial infarction and heart failure, pulmonary hypertension and renal disease. ET production is increased in arterial hypertension remains controversial. Non-peptidic ET antagonists have been developed which either block ETA- receptors or ETA- and ETB-receptors simultaneously. The advantage of ETA-receptors is that they leave the endothelium-dependent vasodilation to ET (via ETB-receptor) intact. However, ETB-mediated contraction remains unaffected by these antagonists. In contrast ETA-/ETB-antagonists fully prevent ET-induced vasoconstriction, however, they also inhibit the endothelial effects of the peptide. ET antagonists interfere with the effects of ET in isolated vascular tissue (including that obtained from humans) as well as in vivo. In humans, ETA as well as ETA-/ETB-antagonists inhibit endothelin-induced vasoconstriction. Hence in summary ET are a family of potent peptides with profound effects in the vasculature. Several studies suggest a role of ET in cardiovascular disease. The newly developed ET-antagonists are potent and selective tools to delineate the (patho-)physiological roles of ET and may become a new class of cardiovascular drugs.
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PMID:Endothelin and endothelin antagonists: pharmacology and clinical implications. 771 86

Ramipril is a second generation angiotensin converting enzyme (ACE) inhibitor. Like enalapril, it is a prodrug and is hydrolysed in vivo to release the active metabolite, ramiprilat, which has a long elimination half-life, permitting once-daily administration. The antihypertensive efficacy of ramipril has been confirmed in large-scale noncomparative studies conducted in general practice as well as in more rigorously controlled clinical trials. In the former, approximately 85% of patients with mild to moderate essential hypertension have responded successfully to treatment with ramipril 2.5 or 5 mg/day, while comparative trials indicate that the antihypertensive efficacy of the drug is equivalent to that of other established ACE inhibitors and the beta-adrenoceptor antagonist atenolol. As expected, the response rate to ramipril monotherapy is lower in patients with severe hypertension (around 40%), although the blood pressure lowering effect can be enhanced with the addition of a diuretic such as hydrochlorothiazide or piretanide. The antihypertensive efficacy of ramipril is maintained in patients with diabetes mellitus and preliminary data indicate that the drug has the beneficial effect of decreasing urinary albumin excretion in diabetic patients with nephropathy. Ramipril is superior to atenolol in causing regression of left ventricular hypertrophy, although the clinical significance of this effect per se remains to be established. The large-scale Acute Infarction Ramipril Efficacy (AIRE) study demonstrated that ramipril 5 or 10 mg/day significantly decreased the risk of all-cause mortality by 27% in patients with clinical evidence of heart failure after acute myocardial infarction, even if transient. The beneficial effect of ramipril was apparent by 30 days of treatment and appeared to be greatest in patients with more severe ventricular damage after infarction. Ramipril is well tolerated in general practice, with 5% or fewer patients discontinuing therapy because of drug intolerance. The data available suggest that ramipril shares a similar tolerability profile to that of other established ACE inhibitors. Thus, clinical data confirm ramipril as a useful alternative ACE inhibitor for the treatment of patients with mild to moderate hypertension, and indicate a beneficial effect of the drug in patients with clinical evidence of heart failure after acute myocardial infarction. It is also reasonable to assume that ramipril will be of value in the treatment of patients with more established heart failure or asymptomatic left ventricular dysfunction.
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PMID:Ramipril. An updated review of its therapeutic use in essential hypertension and heart failure. 777 15

Carvedilol is an arylethanolamine that is a racemic mixture of 2 enantiomers. The S-(-)-enantiomer has beta-adrenoceptor blocking activity, while the racemate also has alpha 1-receptor blocking activity due to the activity of the R-(+)-enantiomer. The drug is rapidly absorbed and undergoes extensive first-pass metabolism in the liver. It reaches a peak concentration 1 to 2 hours postdose and has an elimination half-life of about 4 to 7 hours. Absorption is delayed by food. The drug is highly lipophilic and is highly protein bound. The drug is metabolised by the liver, with some metabolites having biological activity. The pharmacokinetic profile is not altered in the elderly or in patients with renal disease. However, bioavailability of the oral medication is greatly increased in patients with liver disease. Carvedilol lowers blood pressure as a result of its beta-blocking and vasodilatory activity. The reduction in blood pressure is similar to that achieved with other antihypertensive drugs, and there are no adverse effects on renal or cerebral blood flow. Carvedilol has been used in small numbers of patients with cardiac failure. It reduces left ventricular hypertrophy and has no significant adverse metabolic effects.
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PMID:Clinical pharmacokinetics and pharmacodynamics of carvedilol. 791 79

Platelet function, antithrombin and plasminogen activities, and fibrinolytic capabilities in 11 cats with acquired heart disease were compared with results in 4 healthy cats. Of 11 cats with heart disease, 9 had hyperthyroidism with secondary cardiac dysfunction. One cat with hyperthyroidism had renal disease and heart failure, and of 2 cats with idiopathic hypertrophic cardiomyopathy, 1 also had renal disease. At the time of testing, 3 cats had thromboembolic events associated with the disease. Compared with healthy cats, cats with acquired heart disease had increased activity of antithrombin III, a protein that behaves as an acute-phase reactant. Plasminogen activity was decreased, although not significantly, in cats with acquired heart disease, compared with results in healthy cats. In cats with left ventricular dysfunction, clot retraction was decreased (marginal significance, P = 0.058) and might be attributed, in some cases, to the medications received by the cats. Dilute whole blood clots from all cats failed to lyse in vitro. This observation, at present, lacks adequate explanation. Platelets from cats with acquired heart disease, compared with platelets from healthy cats, had decreased responsiveness (aggregation and [14C]serotonin release) to adenosine diphosphate and increased responsiveness to collagen. Hyperthyroid cats were receiving various drugs (propranolol, atenolol, or diltiazem) to empirically treat clinical signs of disease attributable to cardiac dysfunction. Although numbers of cats in each group were small, definite trends were observed in the results of tests. Platelets from cats receiving atenolol had decreased responsiveness to adenosine diphosphate and unaltered responsiveness to collagen, compared with platelets from healthy cats, and may have decreased risk of thrombus formation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Platelet function and antithrombin, plasminogen, and fibrinolytic activities in cats with heart disease. 806 8

A-II exerts its activity on various target tissues by binding to its receptors. The discovery of local RASs and A-II receptors within various tissues has generated interest in the clinical usefulness of RAS inhibition by directly blocking the action of A-II at the receptor level. Different A-II receptor subtypes have been identified and subsequently termed AT1 and AT2. AT1-receptor subtypes are the predominant receptor subtypes existing in most organs and, by coupling to a transmembrane G protein, seem to be the main subtypes participating in the vasoactive responses of A-II. Saralasin, a peptide with specific A-II receptor-antagonistic activity, had limited practical long-term usefulness as a result of its short half-life, significant agonistic properties, and lack of oral bioavailability. The discovery of simple benzyl-substituted imidazoles, which possess weak but highly selective A-II receptor antagonistic properties, led to the development of losartan (DuP 753). Losartan is a potent, orally active, specific, competitive nonpeptide A-II receptor antagonist that appears to be an effective antihypertensive agent both in animal studies and in preliminary clinical trials. The therapeutic usefulness of losartan, however, is not limited to its antihypertensive effects. The potential benefits of A-II receptor antagonists include roles in postmyocardial infarction therapy, slowing A-II-induced cardiac hypertrophy, 154, 155 slowing the progression of heart failure, preventing postangioplasty restenosis, and in slowing the progression of renal disease. Furthermore, losartan, a selective A-II type 1 (AT1) receptor antagonist, has also been a valuable pharmacologic probe for studying the mechanism of A-II stimulation of its receptors. A-II receptor antagonism appears to be as effective as ACE inhibition in the treatment of hypertension and other pathologic processes that involve the RAS and may offer an alternative to those patients who cannot tolerate ACE inhibitors because of their side effects.
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PMID:Angiotensin II receptor antagonists: a new approach to blockade of the renin-angiotensin system. 817 70

A female patient who had open heart surgery for cor triatriatum under hemodialysis, subsequent kidney transplantation and pregnancy is reported. We performed hemodialysis on the patient before, during and after heart surgery to control renal failure. Two years after heart surgery, she received a kidney graft from her mother. The kidney graft showed good function. She was treated with azathioprine and prednisone. Three years after renal transplantation she delivered a healthy male infant by elective Caesarean section at 37 weeks' gestation. Mother and infant did well following delivery. There was lack of hypertension, proteinuria, signs of graft rejection, and recurrence of heart failure during pregnancy. She showed serum creatinine level < 2 mg/dl, a prednisone of < 2 mg/kg/day. Elective Caesarean section has improved hydronephrosis due to the compression of the fetus. The aforementioned good criteria contributed to the successful pregnancy of the renal transplant patient in our experience. We believe early surgical intervention overcomes complicated heart disease even with endstage renal disease, and it gives a chance to receive renal transplantation and have a healthy child. To our knowledge, this is the first report that has described the successful management of open heart surgery under hemodialysis, subsequent renal transplantation and pregnancy in a female patient with chronic renal failure.
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PMID:A case of cor triatriatum with end-stage renal disease: successful management of open heart surgery under hemodialysis, subsequent renal transplantation and pregnancy. 848 11

NSAIDs pose little threat of renal insult in normal, healthy persons at therapeutic dosages. However, NSAID administration to susceptible persons may cause decrements in renal plasma flow and glomerular filtration rate within hours. Such acute noxious renal effects are mediated by products of arachidonic acid metabolism. Precipitous decrements in glomerular filtration and renal ischemia, manifested by increased serum creatinine and urea nitrogen, are possible. However, these effects are usually fully reversible with prompt discontinuation of the offending NSAID. Risk factors for the development of these acute renal effects are known. Acute interstitial nephritis with or without nephrotic syndrome is a rare form of renal toxicity that typically occurs between 2-18 months of use. Renal impairment may be so severe as to require temporary hemodialysis; however, renal function usually returns to normal upon discontinuation of the NSAID. The mechanism of acute interstitial nephritis is presumed to be of allergic origin but could also be caused by a reactive metabolite. Fenoprofen use appears to be associated with a much higher risk for its development. In contrast to the acute effects of NSAIDs, irreversible, analgesic-associated nephropathy manifested by papillary necrosis and chronic interstitial nephritis may occur following months to years of high doses of analgesic mixtures. The mechanism by which combination analgesics produce this form of renal injury is unknown and could be either a result of medullary ischemia or a direct effect of a reactive metabolite. An important issue to be resolved is the relationship between the acute, reversible, prostaglandin-mediated renal effects of the NSAIDs and chronic, irreversible destruction, if such a relationship exists. Theoretically, continual or repeated decrements in renal function in patients with predisposing risk factors could cause or contribute to progressive deterioration in renal function. Elevations in blood pressure or interference with the effects of antihypertensive medications could theoretically also contribute to long-term renal deterioration. In addition to renal syndromes caused by NSAIDs that result in renal impairment, other transient effects on electrolyte and water metabolism may also occur. Reduced secretion of sodium may result in formation of edema, exacerbation of heart failure, or increased blood pressure. Hyporeninemic-hypoaldosteronism may produce hyperkalemia. Finally, reduced excretion of water has rarely caused hyponatremia. It has been suggested that NSAIDs may be renoprotective in patients with nephrotic syndrome. Others have suggested that sulindac is "renal-sparing" because of a unique metabolic pathway that supposedly limits the exposure of the kidney to the active sulfide metabolite.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Renal toxicity of the nonsteroidal anti-inflammatory drugs. 849 47

The aim of the present study was to determine the long-term status of the native aortic valve after surgical treatment of acute aortic dissection involving the ascending aorta. From 1972 to 1991, 93 patients underwent operation for type I or II aortic dissection. There were 76 men and 17 women. Mean age was 54 +/- 13 years. Eighty patients (86%) had a conservative procedure regarding the aortic root and aortic cusps: 74 had prosthetic replacement of the ascending aorta and 6, complete replacement of the aortic arch. Thirteen patients (14%) had simultaneous replacement of the aortic valve and the ascending aorta. The overall hospital mortality rate was 29% (27/93). The overall actuarial survival rate was 60.2% +/- 5.2%, 49.7% +/- 6.1%, and 35.9% +/- 8.1% at 5, 10, and 15 years, respectively. The survival rates for patients who had an ascending aortic procedure only were 63% +/- 5.5%, 54% +/- 6.5%, and 39% +/- 8.5% at 5, 10, and 15 years, respectively, and for patients who required aortic valve replacement, 45% +/- 14% and 22% +/- 17.5% at 5 and 10 years, respectively. Fifty long-term survivors (94% follow-up) with preservation of the aortic valve and aortic root were studied. Among them, 9 (18%) died within a mean interval of 97 +/- 46 months after operation. Causes of death were ischemic cardiac failure (2), aortic rupture or extension of dissection (4), renal disease (1), stroke (1), and sudden death (1). Forty-one patients had long-term clinical and echocardiographic evaluation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Preservation of the aortic valve in acute aortic dissection: long-term echocardiographic assessment and clinical outcome. 851 4

Angiotensin converting enzyme inhibitors (CEI) are logically proposed for the treatment of hypertension and heart failure because of their effect on reducing arteriol resistance. When administered early after myocardial infarction, CEI reduce mortality, particularly patients with severely deteriorated myocardium. Up to 74 lives can be saved for every 1000 patients treated. This beneficial effect is additive with that resulting from aspirin, beta-blockers and fibrinolysis. The effect occurs within the first month of treatment if initiated within the first 24 hours following the infarction, and persists even if treatment is discontinued. Tolerance is generally good, but dosage must be adapted in case of hypotension or temporary renal failure. Macroproteinuric nephropathy in insulin-dependent-diabetes is another indication for CEI. Captopril and enalapril have been shown to slow progression of renal failure and decrease the risk of death and of chronic dialysis. Further studies are being conducted to determine the effect of CEI in non-insulin-dependent diabetes. Finally, experimental arguments suggest that atherosclerosis is partly dependent on the renin/angiotensin system and that CEI might inhibit its development. Most clinical trials evaluating the action of CEI on atheromatosis have studied the effect in the carotid and coronary arteries.
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PMID:[Enzyme converting inhibitors. Current knowledge and perspectives]. 854 40

High blood pressure (BP) in the elderly must not be ignored as a normal consequence of aging. The criteria for the diagnosis of hypertension and the necessity to treat it are the same in elderly and younger patients. The aim of treatment of elderly hypertensive patients is to decrease BP safely and to reduce risk factors associated with cerebrovascular, cardiovascular and renal morbidity and mortality. The treatment of elderly hypertensive patients should be adjusted according to the needs of the individual, based upon age, race, severity of hypertension, co-existing medical problems, other cardiovascular risk factors, target-organ damage, risk-benefit considerations and costs. In addition to the elevated BP, other cardiovascular risk factors include smoking, glucose intolerance, hyperinsulinaemia, dyslipidaemia, hypercreatininaemia, peripheral vascular disease, left ventricular hypertrophy, and microalbuminuria (or albuminuria). Thus, the choice of initial antihypertensive therapy in elderly hypertensive patients should be based not only on the expected response, but also on the effects of therapy on lipid, potassium, glucose and uric acid levels, and left ventricular anatomy and function. Co-existing medical conditions (such as asthma, diabetes mellitus, heart failure, renal failure, gout, coronary artery disease, hyperlipidaemia and peripheral vascular disease) are major determinants for the selection of antihypertensive medications. With previous therapies (diuretics, beta-blockers, etc.), good BP control in the elderly was associated with clear and statistically significant reductions in stroke-related morbidity and mortality, but the overall effects on cardiovascular and renal complications of hypertension was either more variable or less obvious. Angiotensin converting enzyme (ACE) inhibitors are not only efficacious antihypertensive agents in the elderly, but also appear promising in counteracting some of the cardiovascular and renal consequences of hypertension. They are well tolerated and have a relatively low incidence of adverse effects. ACE inhibitors possess ancillary characteristics that are potentially beneficial for many elderly patients, including reduction of left ventricular mass, lack of metabolic and lipid disturbances, no adverse CNS effects, no risk of induction of heart failure, and a low risk of orthostatic hypotension. Since ACE inhibitors may improve perfusion to the heart, kidney and brain, they are well worth considering for the treatment of elderly patients with hypertensive target organ damage, especially in patients with heart failure, and diabetic patients with early nephropathy.
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PMID:ACE inhibitors. Differential use in elderly patients with hypertension. 857 91


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