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)

The goal of this study was to determine whether coronary endothelial function was altered after pacing-induced heart failure in conscious dogs. Fourteen mongrel dogs were chronically instrumented for measurements of systemic hemodynamics, left circumflex coronary artery diameter (CD) and blood flow, and for left ventricular pacing for 4 wk. Heart failure developed during this pacing regimen and was characterized by a significant reduction in arterial pressure, an increase in left atrial pressure, a resting tachycardia, a depression of left ventricular dP/dt to isoproterenol injection, a significant reduction of the slope of the end-systolic pressure-diameter relationship, and all of the characteristic clinical signs. During heart failure, the dilation of CD after release of a brief coronary artery occlusion, acetylcholine, and arachidonic acid was attenuated, whereas prostaglandin (PG) I2- and nitroglycerin-induced dilations of CD were unchanged. The coronary blood flow responses to occlusion, acetylcholine, and nitroglycerin were depressed, but not to PG. Large coronary arteries and microvessels were isolated from normal and failing hearts. Both isolated large coronary arteries and microvessels from failing hearts produced significantly less nitrite, the immediate metabolite of nitric oxide in aqueous solution, than those of normal hearts. Thus endothelium-mediated control of the coronary circulation was depressed during heart failure. A decrease in the production of nitric oxide-endothelium-derived relaxing factor was most likely responsible for this depression.
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PMID:Defective endothelium-mediated control of coronary circulation in conscious dogs after heart failure. 814 68

An enhanced risk for myocardial infarction has been observed in humans with sustained activation of the local and/or systemic renin-angiotensin system, such as a high renin-sodium profile or a heritably enhanced expression of angiotensin converting enzyme. Chronic renin-angiotensin system blockade by angiotensin converting enzyme inhibition reduces the rate of myocardial reinfarction in patients with moderate heart failure. Preliminary experimental evidence suggests that these clinical observations may be partially explained by a proatherogenic effect of an activated renin-angiotensin system, which can downregulate the expression of the endothelial nitric oxide synthase III. Nitric oxide exerts many potentially antiatherogenic effects on endothelium, platelets and low density lipoproteins and indirectly on monocytes and leukocytes Hypertension-induced chronic distension of elastic arteries upregulates the local renin-angiotensin system in these arteries and thereby downregulates nitric oxide synthase. Enhanced local synthesis of the trophic factor angiotensin-II and reduced releasability of the antitrophic factor nitric oxide appear to cooperate in the trophic adaptation of the distended vessel wall to the enhanced load, but with the disadvantage of enhanced susceptibility for atheroma development due to reduced availability of nitric oxide. Chronic blockade of the renin-angiotensin system by angiotensin converting enzyme inhibitors or by angiotensin receptor type-1 antagonists normalizes a reduced endothelial nitric oxide availability in several models, partially by a bradykinin-dependent mechanism. This endothelial protection proved to attenuate the progression of atherosclerosis in experimental models. The antiatherogenic potential of renin-angiotensin system blockade in humans is presently under study.
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PMID:The endothelium and the renin-angiotensin system. 818 13

The endothelium plays an important role in the control of human vascular tone by releasing endothelium-derived nitric oxide. Therefore, endothelial dysfunction could be involved in the increased peripheral vasoconstriction of patients with chronic congestive heart failure (CHF). To investigate endothelial function in humans in vivo, agents such as acetylcholine are used to stimulate the release of endothelium-derived nitric oxide (EDRF). Conversely, N-mono-methyl-L-arginine (L-NMMA), a specific inhibitor of nitric oxide synthesis from L-arginine decreases forearm blood flow by inhibiting the basal release of nitric oxide. Consistent with experimental studies, the blood flow response to acetylcholine is blunted in patients with chronic heart failure as compared to healthy age-matched volunteers. In contrast, the decrease in blood flow induced by L-NMMA appears to be exaggerated in CHF. The blood flow response to nitroglycerin or sodium nitroprusside, endothelium-independent vasodilators, is usually preserved in patients with chronic, non-edematous heart failure, indicating a normal response of the vascular smooth muscle of resistance vessels to exogenous nitric oxide. In contrast, the dilator response of the radial artery diameter to nitroglycerin and flow-dependent dilation are impaired in patients with chronic heart failure, indicating that the abnormal flow-mediated relaxation of large arteries may be due to both endothelial and vascular smooth muscle alterations. Thus, impaired endothelium-dependent dilation of peripheral resistance vessels emerges in chronic heart failure, suggesting a reduced release of nitric oxide upon stimulation. Thus, endothelial dysfunction may be involved in the impaired vasodilator capacity in the peripheral circulation, e.g. during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endothelial dysfunction in chronic heart failure. Experimental and clinical studies. 818 23

After the discovery by Furchgott and colleagues in 1980 that the endothelium plays an obligatory role in acetylcholine-induced vasodilation many investigators have elucidated the role of the endothelium in the regulation of vascular tone. While the sympathetic nervous system serves the organism as a whole, the endothelium appears to act as a local regulator adapting blood flow to local metabolic needs. A variety of endothelium-derived relaxing and contracting factors such as nitric oxide, prostacyclin, endothelium-derived hyperpolarizing factor, endothelin and thromboxane A2 play a role in the endothelium-dependent control of vascular tone. Furthermore, nitric oxide inhibits thrombocyte aggregation and adhesion. Many diseases have been reported to be associated with an impaired endothelium-dependent vasodilation which may contribute to an increased susceptibility to vasospasm, decreased inhibition of thrombus formation and an impaired ability to reduce vascular resistance in ischaemic conditions. In hypertension, hypercholesterolaemia and diabetes mellitus this impairment may be interpreted as an early marker of a process that ultimately will lead to atherosclerosis. The impaired endothelium-dependent vasodilation probably contributes to the increased peripheral vascular resistance in hypertension and heart failure. The role of the endothelium does not seem to be restricted to cardiovascular diseases. Several mediators of inflammation stimulate the endothelium to release nitric oxide, suggesting an important role of the endothelium in the haemodynamic sequelae of sepsis.
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PMID:Endothelium and the regulation of vascular tone with emphasis on the role of nitric oxide. Physiology, pathophysiology and clinical implications. 820 3

Despite the increasing insight in the clinical importance of nitric oxide (NO), formerly known as endothelium-derived relaxing factor (EDRF), there is limited information about the metabolism and elimination of this mediator in humans. We studied the degradation of NO in healthy subjects inhaling 25 ppm for 60 minutes and in patients with severe heart failure inhaling 20, 40, and 80 ppm in consecutive 10-minute periods. In other healthy subjects, the renal clearance of NO metabolite was measured. The metabolism ex vivo was evaluated by direct incubation of nitrite, the NO oxidation product, in blood from healthy humans. During inhalation of NO, the plasma levels of nitrate increased progressively, both in the healthy subjects (from 26 to 38 mumol/L, P < .001) and in the patients (from 72 to 90 mumol/L, P < .001). Methemoglobin (MetHb) also increased in the healthy subjects (from 7 to 13 mumol/L, P < .001) as well as in the patients (from 19 to 42 mumol/L, P < .01). No change in nitrosohemoglobin (HbNO) was detected, either in the healthy subjects or in the patients. In arterialized blood (O2 saturation, 94% to 99%), incubated nitrite was semiquantitatively converted to nitrate and MetHb. In venous blood (O2 saturation, 36% to 85%) moderate amounts of HbNO were also formed. Plasma and urinary clearance of nitrate in healthy subjects averaged 20 mL/min. We conclude that uptake into the red blood cells with subsequent conversion to nitrate and MetHb is a major metabolic pathway for endogenously formed NO. Nitrate may then enter the plasma to be eliminated via the kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Metabolism and excretion of nitric oxide in humans. An experimental and clinical study. 822 83

There is evidence that the endothelium plays an important role in the control of human vascular tone by releasing endothelium-derived nitric oxide and, therefore, a defective endothelial function could be involved in the increased peripheral vasoconstriction of patients with chronic congestive heart failure. To investigate endothelial function in humans in vivo, agents such as acetylcholine, a short-acting stimulator of the release of endothelium-derived nitric oxide, has been used. Conversely, N-mono-methyl-L-arginine, a specific inhibitor of nitric oxide synthesis from L-arginine, has recently been shown to decrease blood flow during infusion into the brachial artery of healthy volunteers (control subjects) by inhibiting the basal release of nitric oxide. Consistent with experimental studies, the blood flow response to acetylcholine is blunted in patients with chronic heart failure compared with healthy age-matched volunteers. In contrast, the decrease in blood flow induced by N-mono-methyl-L-arginine appears to be exaggerated in congestive heart failure. The blood flow response to nitroglycerin or sodium nitroprusside, endothelium-independent vasodilators, is usually preserved in patients with chronic, nonedematous heart failure, indicating a normal response of the vascular smooth muscle of resistance vessels to exogenous nitric oxide. In contrast, the dilator response of the radial artery diameter to nitroglycerin and flow-dependent dilation is impaired in patients with chronic heart failure, indicating that the abnormal flow-mediated relaxation of large arteries may be caused by both endothelial and structural abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endothelial function in congestive heart failure. 836 50

Atrial natriuretic factor (ANF) promotes natriuresis and diuresis, increases vascular permeability and may induce peripheral vasodilatation. Endothelium-derived relaxing factor (EDRF), which is nitric oxide (NO), promotes local vasodilatation. ANF and EDRF-NO both cause vascular relaxation by generating cGMP via the activation of the particulate and soluble guanylate cyclases, respectively. This study examines the in vivo effect of exogenous ANF administration in normal Wistar rats, and of increased endogenous ANF in an experimental model of heart failure, on plasma and tissue cGMP concentrations. Low-dose ANF increased plasma and pulmonary cGMP concentrations, whereas 10-fold higher doses were necessary to increase aorta cGMP concentrations. Rats with a myocardial infarction had increased plasma ANF and cGMP and pulmonary cGMP concentrations, but aorta cGMP concentration remained similar to that of sham-operated rats. NG nitro L-arginine methyl ester (L-NAME) was administered chronically to sham-operated and myocardial infarction rats to block NO-synthase: soluble guanylate cyclase activity. L-NAME did not lower the increase in plasma ANF concentration or in urinary, plasma or pulmonary cGMP concentration. In contrast, L-NAME reduced the aorta cGMP concentration 6-fold, despite an increased level of circulating ANF. In summary, the pathophysiological range of plasma ANF concentrations greatly increases plasma and pulmonary cGMP concentrations (by activating particulate guanylate cyclase), but has little influence on the aorta cGMP concentration (which remains mainly dependent on NO-synthase: soluble guanylate cyclase activity).
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PMID:Atrial natriuretic factor influences in vivo plasma, lung and aortic wall cGMP concentrations differently. 839 39

Nitrates' mechanisms of action are reviewed focusing on are reviewed its hemodynamic effects on the systemic circulation and particularly on the coronary circulation. The beneficial effect of its use is discussed both in angina pectoris and heart failure clinical situations. These drugs mechanisms of action are described, particularly at cellular level, explaining its importance as exogenous suppliers of nitric oxide, and the location of its receptors is discussed. Particular attention is given to the tolerance phenomenon observed when they are used in clinical practice.
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PMID:[Mechanism of action of nitrates]. 849 15

Septic shock is a major cause of hospital deaths despite modern intensive therapy. Profound hypotension is caused by a collapse of regulatory mechanisms. Recent advances have established that bacterial products and the host inflammatory response together generate uncontrolled production of nitric oxide throughout the vasculature, accounting for this vasodilatation. Progressive heart failure is a further manifestation of established septic shock. Emerging research suggests that overproduction of nitric oxide within the myocardium likewise leads to loss of normal myocardial function. The possibility exists that exciting future therapies will be able to selectively inhibit the overproduction of nitric oxide and aid recovery from this frequently lethal condition.
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PMID:Nitric oxide, myocardial failure and septic shock. 853 51

Hypertension is an important cardiovascular risk factor. High blood pressure per se is not a disease but a hemodynamic alteration associated with vascular disease. Two classes of drugs are especially effective in lowering blood pressure and preventing cardiovascular complications, angiotensin converting enzyme (ACE) inhibitors and calcium antagonists. The hemodynamic effects of ACE inhibitors and calcium antagonists are complementary. While ACE inhibitors inhibit the renin-angiotensin system and reduce sympathetic outflow, calcium antagonists dilate large conduit and resistance arteries. Certain calcium antagonists, such as verapamil, lower heart rate. In the blood vessel wall, the local vascular effects of ACE inhibitors and calcium antagonists are also complementary. While ACE inhibitors inhibit activation of angiotensin I into angiotensin II and prevent the breakdown of bradykinin (which stimulates nitric oxide and prostacyclin formation), calcium antagonists inhibit the effects of vasoconstrictor hormones such as angiotensin II at the level of vascular smooth muscle by reducing calcium inflow and facilitating the vasodilator effects of nitric oxide. Calcium antagonists reduce smooth muscle cell proliferation and atherosclerosis. In hypertensive animals, verapamil and trandolapril normalize endothelial dysfunction. In large angiographic trials, nifedipine and nicardipine reduced the development of new atherosclerotic plaques. After myocardial infarction, verapamil reduces mortality and cardiac events in patients without heart failure. In contrast, ACE inhibitors are effective after myocardial infarction in patients with impaired left ventricular function. Urinary albumin excretion rate decreases during ACE inhibitor therapy or with a calcium antagonist such as verapamil; combination of the two drugs has an additive effect. In resistance arteries, hypertension is associated with an increased media/lumen ratio. ACE inhibitors, but not beta-blockers, markedly improve these structural changes. In summary, ACE inhibitors and calcium antagonists have a complementary profile, both in their hemodynamic and local vascular action. Hence, combination therapy with these two classes of drugs appears particularly useful in patients with hypertension, not only to lower blood pressure, but hopefully to achieve improved cardiovascular protection.
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PMID:Vascular protective effects of ACE inhibitors and calcium antagonists: theoretical basis for a combination therapy in hypertension and other cardiovascular diseases. 856 68


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