Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human hypertension affects affects more than 20% of the adult population in industrialized countries, and it is implicated in millions of deaths worldwide each year from stroke, heart failure and ischemic heart disease. Available evidence suggests a major genetic impact on blood pressure regulation. Studies in monogenic hypertension revealed that renal salt and volume regulation systems are predominantly involved in the genesis of these disorders. Mutations here affect the synthesis of mineralocorticoids, the function of the mineralocorticoid receptor, epithelial sodium channels and their regulation by a new class of kinases, termed WNK kinases. It has been learned from monogenic hypotension that almost all ion transporters involved in the renal uptake of Na(+) have a major impact on blood pressure regulation. For essential hypertension as a complex disease, many candidate genes have been analysed. These include components of the renin-angiotensin-aldosterone system, adducin, beta-adrenoceptors, G protein subunits, regulators of G protein signalling (RGS) proteins, Rho kinases and G protein receptor kinases. At present, the individual impact of common polymorphisms in these genes on the observed blood pressure variation, on risk for stroke and as predictors of antihypertensive responses remains small and clinically irrelevant. Nevertheless, these studies have greatly augmented our knowledge on the regulation of renal functions, cellular signal transduction and the integration of both. Together, this provides the basis for the identification of novel drug targets and, hopefully, innovative antihypertensive drugs.
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PMID:Genetics of arterial hypertension and hypotension. 1726 98

Class I recommendations for treating patients with current or prior symptoms of heart failure with reduced left ventricular ejection fraction (LVEF) include using diuretics and salt restriction in individuals with fluid retention. Use angiotensin-converting enzyme (ACE) inhibitors, beta blockers, and angiotensin II receptor blockers if intolerant to ACE inhibitors because of cough or angioneurotic edema. Nonsteroidal anti-inflammatory drugs, most antiarrhythmic drugs, and calcium channel blockers should be avoided or withdrawn. Exercise training is recommended. Implant cardioverter-defibrillator (ICD) is recommended in individuals with a history of cardiac arrest, ventricular fibrillation, or hemodynamically unstable ventricular tachycardia. ICD is indicated in patients with ischemic heart disease for at least 40 d post-myocardial infarction or nonischemic cardiomyopathy, an LVEF of 30% or less, New York Heart Association (NYHA) class II or III symptoms on optimal medical therapy, and an expectation of survival of at least 1 yr. Cardiac resynchronization therapy should be used in individuals with an LVEF of 35% or below, NYHA class III or IV symptoms despite optimal therapy, and a QRS duration greater than 120 ms. An aldosterone antagonist can be added in selected patients with moderately severe to severe symptoms of heart failure who can be carefully monitored for renal function and potassium concentration (serum creatinine should be <or=2.5 mg/dL in men and <or=2.0 mg/dL in women; serum potassium should be <5.0 mEq/L).
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PMID:Treatment of heart failure with decreased left ventricular ejection fraction. 1789 26

Underlying causes and precipitating causes of heart failure (HF) should be treated when possible. Persons with HF and normal left ventricular ejection fraction (LVEF) should have maintenance of sinus rhythm, treatment of hypertension, myocardial ischemia, dyslipidemia, and anemia, slowing of the ventricular rate below 90 bpm, 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 and angiotensin-converting enzyme (ACE) inhibitors. If persons are unable to tolerate ACE inhibitors because of cough, angioneurotic edema, rash, or altered taste sensation, angiotensin II type I receptor antagonists (ARBs) should be given. If HF persists despite diuretics, beta blockers, and ACE inhibitors or ARBs, isosorbide dinitrate plus hydralazine should be administered. Beta blockers, verapamil, diltiazem, and digoxin may be used to slow a rapid ventricular rate in persons with supraventricular tachyarrhythmias. Digoxin should not be used in persons with HF in sinus rhythm with normal LVEF. Exercise training should be encouraged in persons with mild to moderate HF to improve functional status and to decrease symptoms.
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PMID:Treatment of heart failure with normal left ventricular ejection fraction. 1802 14

The activation of cardiac cell membrane ATP-sensitive potassium channels during myocardial ischemia promotes potassium efflux, reductions in action potential duration, and heterogeneities in repolarization, thereby creating a substrate for re-entrant arrhythmias. Drugs that block this channel should be particularly effective anti-arrhythmic agents. Indeed, non-selective ATP-sensitive potassium channel antagonists, (e.g., glibenclamide) can prevent arrhythmias associated with myocardial ischemia. However, these non-selective antagonists have important non-cardiac actions that promote insulin release and hypoglycemia (pancreatic beta-cells), reduce coronary blood flow (vascular smooth muscle cells), prevent ischemia preconditioning (cardiac mitochondrial channels) and depress cardiac contractile function. The ATP-sensitive potassium channel consists of a pore forming inward rectifying potassium channel (Kir6.1 or Kir6.2) and a regulatory subunit (sulfonylurea receptors, SUR1, SUR2A &SUR2B). The Kir6.2/SUR2A combination appears to be preferentially expressed on cardiac cell membranes. As such, it should be possible to develop agents selective for cardiac sarcolemmal ATP-sensitive potassium channels. The novel compounds HMR 1883 (or its sodium salt HMR 1098) or HMR 1402 have been shown to block selectively the cardiac sarcolemmal ATP-sensitive potassium channels. These drugs attenuated ischemically-induced changes in cardiac electrical properties and prevented malignant arrhythmias without the untoward effects of other drugs. Since the ATP-sensitive potassium channel only becomes active as ATP levels fall, these drugs have the added advantage that they would have effects only on ischemic tissue with little or no effect noted on normal tissue. Thus, selective antagonists of the cardiac cell surface ATP-sensitive potassium channel may represent a new class of ischemia selective anti-arrhythmic medications.
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PMID:The cardiac sarcolemmal ATP-sensitive potassium channel as a novel target for anti-arrhythmic therapy. 1870 91

The blood pressure lowering effect of a fruit and vegetable-rich diet is a necessary dietary lifestyle measure now included the guidelines for the management of arterial hypertension. Furthermore, flavonoids represent a major class of plant polyphenolics. The present review addresses the antihypertensive effect of quercetin, one of the most abundant flavonoids present in fruits and vegetables, and probably the best studied flavonoid because of its high biological activity. Quercetin has been shown to induce a progressive, dose-dependent and sustained reduction in blood pressure when given chronically in several rat models of hypertension, including spontaneously hypertensive rats, L-NAME-treated rats, DOCA-salt hypertensive rats, two-kidney one-clip Goldblatt rats, rats with aortic constriction and Dahl salt-sensitive hypertensive rats. Quercetin was also effective in reducing blood pressure in rat models of metabolic syndrome, including the obese Zucker rats as well as rats treated with a high-sucrose, high-fat diet. Quercetin also prevented morphological and functional changes in the heart, vessels and kidney, while increasing production of reactive oxygen species associated with hypertension. A high dose of quercetin also reduced blood pressure in stage 1 hypertensive patients in a randomized, double-blind, placebo-controlled, crossover study. Since raised blood pressure is the major cause of stroke as well as an important risk factor for ischemic heart disease, we propose that the blood pressure-lowering effect of quercetin could be an important mechanism contributing to the reduced risk of myocardial infarction and stroke observed with fruit and vegetables-rich diets, and possibly with flavonoid-rich diets.
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PMID:Antihypertensive effects of the flavonoid quercetin. 1930 94

Intracellular calcium ions (Ca2+) are the key regulators in cardiac and arterial functions during the contraction-relaxation cycle. Myocyte Ca2+ imbalance thus produces mechanical dysfunction, electrical instability (arrhythmia) and muscle remodeling. The sodium-calcium exchanger (NCX) is one of the major Ca(2+)-handling proteins in myocytes. Evidence is currently accumulating to suggest that NCX1 is upregulated in various cardiovascular diseases. Recently developed benzyloxyphenyl NCX inhibitors effectively prevent myocardial ischemia/reperfusion injury and salt-sensitive hypertension in animal models. Furthermore, several experiments with genetically engineered mice provide compelling evidence that these diseases are triggered by pathologic Ca2+ entry through NCX1 in cardiac and arterial myocytes, respectively. Thus, NCX inhibitors may have therapeutic potential as novel cardiovascular drugs for myocardial reperfusion injury and salt-sensitive hypertension. However, the efficacy of NCX inhibitors, as well as the role of NCX1, in heart failure or arrhythmias requires more detailed study.
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PMID:Sodium-calcium exchange inhibitors: therapeutic potential in cardiovascular diseases. 1980 53

Monocyte chemoattractant protein-1 (MCP-1), one of the key inflammatory chemokines, plays an important role in the initiation of atherosclerosis, and represents a risk for coronary artery disease and myocardial infarction. A recent animal study showed that MCP-1 gene might be a candidate gene for salt-sensitive hypertension in Dahl salt sensitive rats. This effect has not been yet studied in asymptomatic humans. We tested the MCP-1 -2518 A/G single nucleotide polymorphism (SNP) in 66 hypertensive ischemic heart disease asymptomatic subjects. Inflammatory markers, classic risk factors and absolute cardiovascular risk (SCORE system) were also investigated in these subjects. Our results showed that both, systolic and diastolic values of blood pressure were associated with MCP-1 -2518 A/G SNP at the level of both, genotype and allele frequencies. Subjects with mutant G allele had higher levels of both values of blood pressure, systolic (p = 0.035) and diastolic (p = 0.040) than subjects with allele A. Statistically significantly higher levels of both values of blood pressure, systolic (p = 0.037) and diastolic (p = 0.021) were found also in IHD asymptomatic subjects with AG and GG genotypes. Subjects with AG and GG genotypes had also an increased absolute cardiovascular risk (1.62% vs 3.17%; p = 0.004) and an increasing trend for elevated plasma level of high-sensitive CRP (2.858 vs 2.062 mg/l; p = 0.076). We did not find any significant correlation between the serum level of MCP-1 and blood pressure. To our best knowledge, this is the first study concerning the association between MCP-1 polymorphism and arterial blood pressure in IHD asymptomatic subjects. These results indicate that the expression of MCP-1 may be increased before the onset of hypertension but further observations from larger cohorts are needed to confirm this finding (Tab. 6, Ref. 41).
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PMID:MCP-1 -2518 A/G gene polymorphism is associated with blood pressure in ischemic heart disease asymptomatic subjects. 2103 20

Review oral modified release drug forms of beta-adrenoblocker metoprolol which is used in arterial hypertension and ischemic heart disease is presented. Metoprolol has salts such as tartrate which is used for production of immediate release (IR) and sustained release (SR) forms and succinate used for production of controlled release form (CR/XL). Metoprolol SR has monolith matrix type, metoprolol CR/XL-system of multiple pellets. Effect of metoprolol tartrate (IR) on mortality was demonstrated in a number of studies in patients with arterial hypertension (AH) (MAPHY), myocardial infarction (SMT, GMT, MIAMI), dilated cardiomyopathy and heart failure (MDC). Studies of efficacy of metoprolol SR are scarce. Antihypertensive efficacy of metoprolol SR in patients with AH did not exceed that of a metoprolol IR or CR/XL. First retrospective analysis of efficacy of metoprolol tartrate and succinate (CR/XL) in patients after myocardial infarction allowed to obtain comparable results of 34% mortality lowering. In a prospective study in patients with chronic heart failure (COMET) metoprolol tartrate IR was not superior to carvedilol when mortality lowering was concerned. At the same time administration of controlled release metoprolol (CR/XL) in 2 large clinical trials (RESOLVD, MERITAHF) was advantageous in patients with chronic heart failure relative to lowering of mortality and rate of hospitalizations. A novel controlled release form of metoprolol has been created as a tartrate salt on the basis of pellet technology (CD/ERT) and its bioequivalence to metoprolol CR/XL has been proved.
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PMID:[Evolution of oral drug forms of metoprolol: advantages of long acting modified release forms with modified release]. 2159 98

The renin-angiotensin system (RAS) plays an important role in regulating blood pressure, water-salt balance and the pathogenesis of cardiovascular diseases. Angiotensin II (Ang II) is the physiologically active mediator and mediates the main pathophysiological actions in RAS. Ang II exerts the effects by activating its receptors, primarily type 1 (AT1R) and type 2 (AT2R). Most of the known pathophysiological effects of Ang II are mediated by AT1R activation. The precise physiological function of AT2R is still not clear. Generally, AT2R is considered to oppose the effects of AT1R. Lectin-like oxidized low-density lipoprotein scavenger receptor-1 (LOX-1) is one of the major receptors responsible for binding, internalizing and degrading ox-LDL. The activation of LOX-1 has been known to be related to many pathophysiological events, including endothelial dysfunction and injury, fibroblast growth, and vascular smooth muscle cell hypertrophy. Many of these alterations are present in atherosclerosis, hypertension, and myocardial ischemia and remodeling. A growing body of evidence suggests the existence of a cross-talk between LOX-1 and Ang II receptors. Their interplays are embodied in the reciprocal regulation of their expression and activity. Their interplays are involved in a series of signals. Recent studies suggests that reactive oxygen species (ROS), nitric oxide (NO), protein kinase C (PKC) and mitogen activated protein kinases (MAPKs) are important signals responsible for their cross-talk. This paper reviews these aspects of dyslipidemia and RAS activation.
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PMID:LOX-1 and angiotensin receptors, and their interplay. 2186 Oct 69

The incidence of cardiovascular events in hypertensive patients is clearly related to a left ventricular mass during treatment, and a regression of left ventricular hypertrophy is associated with a better prognosis. This is the case even independently of changes in other risk factors, including blood pressure. Evidence indicates that lifestyle modifications such as dietary salt restriction and weight loss are effective means in preventing the development of hypertension and reducing blood pressure and left ventricular mass in hypertensive patients. Salt restriction may also reduce the long-term risk of cardiovascular events. It has been recognized that the primary targets of current antihypertensive drugs are the renin-angiotensin-aldosterone system, calcium homeostasis, the ionic transport mechanisms in the kidneys, and the sympathetic nervous system. Clinical as well as experimental studies have demonstrated the cardioprotective effects of antihypertensive drugs independently of their blood pressure lowering effects. Hypertension is often complicated by other disease states including diabetes, dyslipidemia, and ischemic heart disease. Some of the drugs used for the treatment of such complications are also shown to produce cardioprotective effects in addition to their original effects. We ought to better understand these pleiotropic effects for the most effective treatments of hypertension and its complications.
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PMID:Cardioprotective mechanisms of lifestyle modifications and pharmacotherapies on cardiac remodeling and dysfunction in hypertensive heart disease: an overview. 2192 91


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