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)

Urotensin I, a vasoactive peptide isolated from fish urophyses, has previously been demonstrated to cause specific mesenteric dilation in the dog. This mechanism of action should limit its maximal cardiovascular actions: no additional cardiovascular effects should ensure once maximal mesenteric vasodilation is achieved. Provided that the mesenteric vasodilatation does not result in decreased flow to other organs, the agent may, therefore, offer a theoretical advantage as an afterload reducing agent. In pentobarbital anesthetized dogs which were in heart failure as a result of chronic aortico -- left atrial shunt, the effects of urotensin I on cardiovascular hemodynamics were compared with the effects of a nonspecific vasodilator, sodium nitroprusside. At equidepressor doses (approximately 15% decrease in mean arterial pressure; sodium nitroprusside, 2 micrograms . kg-1 . min-1 i.v.; urotensin I, 10 mU . kg-1 . min-1 i.v.), both agents produced comparable falls in total peripheral resistance, left ventricular end diastolic pressure, and pulmonary capillary wedge pressure. Forward cardiac output was increased by both substances, although the increases were not statistically significant. Shunt flow, estimated by echocardiography, was reduced by both. In spite of the marked similarity in hemodynamic effects in this model, the two agents affected regional blood flows differently. Sodium nitroprusside did not significantly alter regional flows measured by radioactive microspheres, although calculated splanchnic, skin, and myocardial vascular resistances were reduced. In contrast, urotensin I, as in the normal dog, greatly increased mesenteric blood flow; this redistribution of cardiac output did not, however, result in underperfusion of other vital organs. These data suggest that urotensin I may be a useful agent in the reduction of afterload in heart failure, particularly since the unique mechanism of action appears to minimize the potential for adverse effects due to excessive dosage.
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PMID:Effect of a specific and a nonspecific vasodilator on regional blood flows in experimental heart failure. 708 66

This study examined the peripheral endothelium-dependent vasodilatory response to acetylcholine and the endothelium-independent vasodilatory response to nitroprusside in 19 patients with chronic heart failure and eight controls. These peripheral blood flow responses were compared with hyperemic calf blood flow changes after maximum leg exercise and 5-min femoral occlusion. The peripheral blood flow response to forearm intra-arterial infusion of acetylcholine and sodium nitroprusside, and reactive hyperemic calf blood flow changes were measured by plethysmography. All peripheral blood flow responses were significantly reduced in patients with chronic heart failure (P < 0.05). Reduction of acetylcholine-mediated changes in peripheral blood flow was correlated with exercise-induced calf blood flow response (r = 0.51, P < 0.05), but not with occlusion-induced calf blood flow response (r = 0.02, NS). Sodium nitroprusside-mediated changes were not correlated with any reactive hyperemic blood flow responses (exercise: r = 0.27, NS; occlusion: r = 0.11, NS). When the patients were divided into two subgroups based on the median exercise-induced calf blood flow change, the subgroup with the lower calf blood flow response showed a reduction in exercise capacity (anaerobic threshold: 11.8 +/- 0.6 vs. 14.6 +/- 1.0 ml/kg/min; P < 0.05). These findings suggest that endothelial dysfunction is related to a decrease in exercise-induced skeletal muscle blood flow and exercise capacity in patients with chronic heart failure.
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PMID:Impaired cholinergic peripheral vasodilation and its relationship to hyperemic calf blood flow response and exercise intolerance in patients with chronic heart failure. 777 92

Effects of carperitide (alpha-human atrial natriuretic peptide) on hemodynamics and renal function in dogs with congestive heart failure (CHF) produced by volume expansion and ligation of the left anterior descending coronary artery were compared with those of various anti-heart failure agents (cardiotonic, vasodilator and diuretic). Carperitide (0.1-1 microgram/kg/min) dose-dependently decreased the elevated left ventricular end-diastolic pressure (LVEDP). No significant changes in cardiac contractility (LV dP/dtmax) and heart rate (HR) were noted, although cardiac output (CO) tended to reduce during the infusion of carperitide. Nitroglycerin (NG; 3 micrograms/kg/min) and furosemide (1 mg/kg) also decreased LVEDP, but the potency was less than that of carperitide. Sodium nitroprusside (SNP; 10 micrograms/kg/min) and dobutamine (10 micrograms/kg/min) caused a reduction in LVEDP and increased CO with an increase in HR. Hydralazine (H; 100 micrograms/kg/min) increased CO without reduction in LVEDP and induced a pronounced increase in HR. Double product (systolic blood pressure x HR), an index of myocardial oxygen consumption, was significantly reduced by carperitide, but significantly increased by DB and H. Carperitide, unlike NG, SNP, H and DB, increased urine volume and urinary electrolyte excretion. These results suggest that carperitide will be an useful therapeutic agent for the treatment of CHF.
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PMID:[Effects of carperitide (alpha-human atrial natriuretic peptide) on acute congestive heart failure in dogs]. 851 7

Sodium nitroprusside is used to treat hypertensive emergencies and acute heart failure. It acts by releasing nitric oxide (NO), a highly potent vasodilator, but unfortunately, for each NO molecule released, five cyanide ions are released. Thus, nitroprusside therapy is limited by cyanide toxicity. Therefore, a cyanide scavenger could be beneficial when administering nitroprusside. Hydroxocobalamin, which has a relatively high binding affinity for cyanide, has been shown to reduce cyanide levels in nitroprusside-treated patients. Cobinamide, the penultimate precursor in hydroxocobalamin biosynthesis, has a much greater affinity for cyanide than cobalamin, and binds two cyanide ions. We now show that cobinamide is highly effective in neutralizing cyanide ions released by nitroprusside in cultured mammalian cells, Drosophila melanogaster, and mice. Cobinamide also binds NO, but at molar concentrations 2.5-5 times that of nitroprusside, it did not decrease NO concentrations or the physiological effectiveness of nitroprusside. We conclude that cobinamide could be a valuable adjunct to nitroprusside therapy.
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PMID:The cobalamin precursor cobinamide detoxifies nitroprusside-generated cyanide. 1752 71

Sodium nitroprusside is an older intravenous vasodilator appropriate for acute hospital treatment of patients with congestive heart failure. It is a balanced arterial and venous vasodilator with a very short half-life, facilitating rapid titration. In general, it improves hemodynamic and clinical status by reducing systemic vascular resistance, left ventricular filling pressure, and increasing cardiac output. This review summarizes recently published literature and recent data regarding the use of this intravenous vasodilator in decompensated heart failure patients.
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PMID:Nitroprusside in decompensated heart failure: what should a clinician really know? 1972 60

Endothelial dysfunction associated with decreased nitric oxide (NO) bioactivity is a major feature of vascular diseases such as atherosclerosis or diabetes. Sodium nitroprusside (SNP)-induced relaxation is entirely dependent on cyclic guanosine monophosphate (cGMP) and preserved in atherosclerosis, suggesting that smooth muscle response to NO donor is intact. However, NO gas activates both cGMP-dependent and -independent signal pathways in vascular smooth muscle cells, and oxidative stress associated with vascular diseases selectively impairs cGMP-independent relaxation to NO. Sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA), which regulates intracellular Ca(2+) levels by pumping Ca(2+) into store, is a major cGMP-independent target for NO. Physiological levels of reactive nitrogen species (RNS) S-glutathiolate SERCA at Cys674 to increase its activity, and the augmentation of RNS in vascular diseases irreversibly oxidizes Cys674 or nitrates tyrosine residues at Tyr296-Tyr297, which are associated with loss of function. S-glutathiolation of various proteins by NO can explain redox-sensitive cGMP-independent actions, and oxidative inactivation of target proteins for NO can be associated with the pathogenesis of cardiovascular diseases. Oxidative inactivation of SERCA is also implicated with dysregulation of smooth muscle migration, promotion of platelet aggregation, and impairment of cardiac function, which can be implicated with restenosis, pathological angiogenesis, thrombosis, as well as heart failure. Analysis of posttranslational oxidative modifications of SERCA and the preservation of SERCA function can be novel strategies against cardiovascular diseases associated with oxidative stress.
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PMID:Modulation of vascular sarco/endoplasmic reticulum calcium ATPase in cardiovascular pathophysiology. 2093 2

Multiple drugs are used for reversibility testing of pulmonary hypertension (PH) in advanced heart failure (HF), especially in the process of heart transplant evaluation. Effects of these drugs were never systematically compared. The aim of this meta-analysis was to compare hemodynamic effects of different drugs. We identified 20 prospective studies reporting hemodynamic variables before and after acute pharmacologic testing for PH reversibility in patients with advanced HF. The data from individual studies were grouped by an outcome measure and analyzed. A mixed model meta-analysis was performed using SAS to give weighted mean effect of pre- and post-test change and inverse variance. The mean effects were weighted by the published sample size. Prostacyclin, inhaled or intravenous, and prostaglandin E1 (PGE1) had the most potent effect on pulmonary vascular resistance (PVR). Sodium nitroprusside and nitroglycerin decreased pulmonary capillary wedge pressure (PCWP), and mean pulmonary arterial pressure (MPAP) better than other drugs. Sildenafil provided overall good hemodynamic outcomes but was not the strongest drug with regard to any particular outcome. PCWP, MPAP, and systolic pulmonary arterial pressure respond better to nitroglycerin and sodium nitroprusside than to other drugs in the setting of reversibility testing. Prostacyclin and PGE1 are superior to other drugs in their acute effects on PVR.
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PMID:Comparison of drugs for pulmonary hypertension reversibility testing: A meta-analysis. 2401 42

Sodium nitroprusside has been used in clinical practice as an arterial and venous vasodilator for 40 years. This prodrug reacts with physiologic sulfhydryl groups to release nitric oxide, causing rapid vasodilation, and acutely lowering blood pressure. It is used clinically in cardiac surgery, hypertensive crises, heart failure, vascular surgery, pediatric surgery, and other acute hemodynamic applications. In some practices, newer agents have replaced nitroprusside, either because they are more effective or because they have a more favorable side-effect profile. However, valid and adequately-powered efficacy studies are sparse and do not identify a superior agent for all indications. The cyanide anion release concurrent with nitroprusside administration is associated with potential cyanide accumulation and severe toxicity. Agents to ameliorate the untoward effects of cyanide are limited by various problems in their practicality and effectiveness. A new orally bioavailable antidote is sodium sulfanegen, which shows promise in reversing this toxicity. The unique effectiveness of nitroprusside as a titratable agent capable of rapid blood pressure control will likely maintain its utilization in clinical practice for the foreseeable future. Additional research will refine and perhaps expand indications for nitroprusside, while parallel investigation continues to develop effective antidotes for cyanide poisoning.
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PMID:Sodium nitroprusside in 2014: A clinical concepts review. 2542 68


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