Search PubMed⌕ Search

Biomedical subjects

H Drexler

Publications and source records attributed to H Drexler.

At least 145 records · Page 8Linked to original sources
PubMed1994

Carbon disulphide. I. External and internal exposure to carbon disulphide of workers in the viscose industry.

Carbon disulphide (CS2), a reagent of rayon production, is known for its high toxic potential and has therefore been the subject of many clinical studies. The aims of the study presented here were to determine the effective exposure to CS2 and to compare the validity of the different exposure indicators. Internal and external exposure to CS2 was investigated in 362 male workers of a viscose factory. The CS2 air concentrations measured through stationary air monitoring in five different work areas (n = 39) were compared with the values of active personal air monitoring (n = 51) and passive personal air monitoring (n = 352). In addition, in all investigations biological monitoring was carried out by measuring the 2-thio-1,3- thiazolidine-carboxylic acid (TTCA) excretion in urine. A significant correlation was found between the data for active and passive personal air sampling (y = 0.99, x + 0.31, r = 0.968). The results of the stationary measurements led, however, to values which were systematically too low. The validity of TTCA excretion in urine as a parameter of biological monitoring could for the first time be verified in a large sample of subjects. There was a linear correlation between TTCA values in the urine related to both volume and creatinine [y (TTCAmg/g creatinine) = 0.315 x (ml CS2/m3 air) + 0.59] and the CS2 values in the air. Nevertheless, TTCA excretion proved to be dependent upon creatinine so that the excreted amounts related to creatinine described the individual exposure more exactly.

Adult↗
PubMed1994

Detection and clinical relevance of a type I allergy with occupational exposure to hexahydrophthalic anhydride and methyltetrahydrophthalic anhydride.

Hexahydrophthalic anhydride (HHPA) and methyltetrahydrophthalic anhydride (MTHPA) belong to the group of the acid anhydrides and, among other applications, are used in the production of epoxy resins. These substances are known as potent low-molecular allergens and induce predominantly type I allergies according to Coombs and Gell. We examined 110 employees exposed to HHPA and MTHPA. With all of them a RAST was carried out with the commercially available conjugates of phthalic anhydride (PA) and a skin prick test with 1% and 5% acetonic solutions of PA. In 109 of these sera a radio allergo sorbent test (RAST) was carried out with the not commercially available conjugates of HHPA and of MTHPA. With complaints connected with the workplace the working materials used (HHPA, MTHPA) were also checked by means of the skin prick test. With at least one positive immunological finding (in the RAST and/or skin prick test) in connection with complaints at the workplace, we performed a workplace-related inhalation test under experimental conditions. Specific IgE against acid anhydrides was detected in a total of 17 (15.4%) persons. In the challenge test, six (5.4%) sensitisations were shown to be clinically relevant. On inclusion of borderline positive findings with PA conjugates the RAST produced three false negative and one false positive finding compared with a RAST with HHPA and MTHPA conjugates. With the conjugates of trimellitic anhydride, in no case could specific IgE be detected. The skin prick test led, in comparison with the RAST, to three false positive and three false negative findings.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Dietary arginine prevents atherogenesis in the coronary artery of the hypercholesterolemic rabbit.

OBJECTIVES: This study was designed to test the hypothesis that long-term oral supplementation of dietary L-arginine (to provide a sustained elevation of nitric oxide activity) would inhibit atherogenesis in hypercholesterolemic rabbits, as assessed by histomorphometric measurements. BACKGROUND: Endothelium-derived nitric oxide inhibits a number of processes that are critical in atherogenesis. Hypercholesterolemia reduces endothelial nitric oxide activity, and we postulate that this may promote atherogenesis. This reduction in nitric oxide activity can be reversed acutely by intravenous infusion of L-arginine, the precursor of nitric oxide. We show that dietary supplementation of L-arginine abrogates the development of coronary atheroma in hypercholesterolemic rabbits. METHODS: Male New Zealand White rabbits were fed normal rabbit chow, 1% cholesterol chow or 1% cholesterol chow with dietary arginine or methionine supplementation to increase their intake of these amino acids sixfold. After 1 or 10 weeks of dietary intervention, the left main and left anterior descending coronary arteries were harvested for histologic study. Plasma cholesterol measurements were elevated to the same degree in all groups of rabbits receiving the 1% cholesterol diet, whereas plasma arginine levels were doubled in the arginine-treated group. High density lipoprotein (HDL) cholesterol values were not affected by arginine treatment. RESULTS: In rabbits receiving the 1% cholesterol diet, with or without methionine supplementation, light and electron microscopy revealed a marked increase from 1 to 10 weeks in the intimal accumulation of macrophages, associated with an increase in the intimal area of the left main coronary artery. By contrast, in arginine-treated hypercholesterolemic rabbits, there was a near absence of adherent monocytes and tissue macrophages and no progression of intimal thickness from 1 to 10 weeks. CONCLUSIONS: Dietary supplements of L-arginine prevent intimal thickening in the coronary arteries of hypercholesterolemic rabbits. This antiatherogenic effect is not due to an alteration in plasma total cholesterol, HDL cholesterol or caloric or nitrogen balance. The data are consistent with the hypothesis that nitric oxide has antiatherogenic properties.

Animals↗
PubMed1994

Pathophysiology and treatment of congestive heart failure.

Pharmacotherapy of heart failure is likely to be most efficacious when individually tailored to the prevailing pathophysiological derangements. Their diagnostic definition and understanding of the mechanisms involved affords the greatest opportunity for their correction and retardation of further progression of the syndrome, together with related improvements in quality of life, reduction of morbid cardiovascular events and improvement in prognosis. Four approaches may be identified, each of which allows rational therapeutic intervention. The disordered contractile geometry of the failing ventricle gives rise to increased ventricular wall tension and myocardial hypertrophy. The phenotype change largely responsible for this progression may be retarded, halted, or even reversed by a reduction of the elevated ventricular pressure and volume induced by diuresis and/or systemic vasodilatation. Knowledge of the subcellular changes responsible for electromechanical coupling and subsequent myocardial cell contraction in the various stages of heart failure is still incomplete. Pharmacotherapeutic interventions with positive inotropic agents have not been universally clinically efficacious, though the digitalis glycosides and, more recently, drugs that increase the sensitivity of the contractile proteins to calcium appear to afford further opportunity as they do not increase myocardial energy expenditure. In this regard, reduction in heart rate is a major determinant of myocardial contractile performance. Vascular stiffness and reduced vasodilator capacity are intrinsic accompaniments of congestive heart failure and exert deleterious effects on the heart by increasing preload and afterload and on the regional circulations by reducing blood flow. The mechanisms responsible include increased activity of the sympathoadrenal and renin-angiotensin-aldosterone systems, as well as reduction of endothelium-derived relaxing factor and increased stiffness of the vascular wall due to oedema.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Vessels↗
PubMed1994

Effect of L-arginine on coronary endothelial function in cardiac transplant recipients. Relation to vessel wall morphology.

BACKGROUND: Coronary endothelial vasodilator dysfunction is a common finding in cardiac transplant recipients and may represent an early marker for the development of intimal thickening and graft atherosclerosis. The present study tested the hypothesis that endothelial dysfunction precedes intimal thickening and that administration of L-arginine, the precursor of endothelium-derived relaxing factor, improves endothelial vasodilator function of coronary conduit and resistance vessels if given at an early stage of graft atherosclerosis. METHODS AND RESULTS: Acetylcholine (10(-6), 10(-5), 10(-4) mol/L) was infused into the left anterior descending or circumflex artery and repeated after intravenous infusion of L-arginine (10 mg.kg-1.min-1 over 20 minutes) in 18 cardiac transplant recipients. Epicardial responses were evaluated by quantitative angiography, and the microcirculation was studied by determination of coronary blood flow with a Doppler flow velocity wire. Intimal thickening was assessed by intravascular ultrasound (n = 14). In epicardial coronary arteries, acetylcholine tended to elicit vasoconstriction. Epicardial coronary vasoconstriction elicited by acetylcholine was attenuated by infusion of L-arginine (10(-4) mol/L, -6.8% versus -2.8%; P < .01); this beneficial effect was observed predominantly in patients with normal intravascular ultrasound characteristics. In coronary resistance vessels, acetylcholine induced vasodilation, reflected by increases in coronary blood flow. The acetylcholine-induced increase in blood flow was significantly enhanced with L-arginine (at a dose of 10(-4) mol/L, + 121% versus 176%; before versus after L-arginine, P < .002). CONCLUSIONS: The coronary vasculature of cardiac transplant recipients exhibits a generalized endothelial dysfunction of conduit and resistance vessels. L-Arginine improves endothelial dysfunction of both coronary microvasculature and epicardial coronary arteries. The reversibility of epicardial endothelial dysfunction by L-arginine is more likely in vessels with normal wall morphology.

Acetylcholine↗
PubMed1994

Enhanced endothelial adhesiveness in hypercholesterolemia is attenuated by L-arginine.

BACKGROUND: We have shown that chronic administration of the nitric oxide (NO) precursor L-arginine normalizes NO-dependent vasodilation and markedly inhibits atherogenesis in a hypercholesterolemic rabbit model. We hypothesized that this antiatherogenic effect is due to modulation of endothelial adhesiveness by endothelium-derived NO. METHODS AND RESULTS: New Zealand White rabbits were fed normal chow (Cont), a high-cholesterol diet (Chol), a high-cholesterol diet supplemented with L-arginine (Arg), or a normal diet supplemented with the NO synthase antagonist L-nitroarginine (L-NA) for 2 weeks. In additional studies, some animals receiving L-NA were also treated with hydralazine to normalize blood pressure. After 2 weeks, thoracic aortas were harvested, opened longitudinally, and placed in a culture dish with the endothelial surface exposed to medium containing WEHI 78/24 cells, a monocytoid cell line. After incubation with the monocytoid cells for 30 minutes on a rocking platform, the aortic segments were washed repeatedly to remove nonadherent cells and adherent cells counted by epifluorescent microscopy. Monocytoid cell binding to aortic endothelium was significantly increased in Chol (P < .001 versus Cont); binding was markedly reduced in arginine-fed hypercholesterolemic animals (P < .05, Arg versus Chol). Monocytoid cell binding to aortic endothelium was also significantly increased in L-NA (P < .05); hydralazine normalized blood pressure but did not reduce monocytoid cell binding. To confirm that alterations in NO activity modulate endothelial cell-monocyte interaction, the release of nitrogen oxides (NOx) by thoracic aortas was assessed by a chemiluminescent technique. The concentration of NOx in the conditioned medium from segments of Arg thoracic aortas was significantly greater than that from Cont aortas, whereas that from L-NA aortas was significantly less. CONCLUSIONS: Hypercholesterolemia enhances the adhesiveness of aortic endothelium for monocytes; this effect is attenuated by dietary L-arginine. Conversely, inhibition of NO synthesis enhances monocyte binding. The results suggest that endothelium-derived NO plays an important role in regulating the endothelial adhesiveness for monocytes. Alterations in NO activity may play a critical role in atherogenesis.

Animals↗
PubMed1994

Comparative effects of chronic angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade on cardiac remodeling after myocardial infarction in the rat.

BACKGROUND: After myocardial infarction, the noninfarcted left ventricle develops reactive hypertrophy associated with a depressed coronary flow reserve, myocardial interstitial fibrosis, and reduced capillary density. The present study investigated the comparative cardiac effects of chronic angiotensin-converting enzyme (ACE) inhibition and selective angiotensin II type 1 receptor (AT1) blockade in the rat model of myocardial infarction and failure. METHODS AND RESULTS: Seven days after coronary ligation (MI), rats were randomized to enalapril (n = 8; 500 micrograms.kg-1.d-1), losartan (n = 9; 3 mg.kg-1.d-1), or placebo (n = 8) and treated for 6 weeks. Sham-operated rats (n = 10) served as controls. Coronary blood flow was measured with radiolabeled microspheres during baseline and maximal coronary dilation induced by dipyridamole (2 mg.kg-1.min-1 over 10 minutes). Right and left ventricular (LV) weight was increased in infarcted rats compared with sham-operated animals and enalapril- and losartan-treated MI rats. Minimal LV and right ventricular coronary vascular resistance was increased in MI rats but normalized with enalapril and losartan (LV:sham, 8.9; MI-placebo, 12.7; MI-enalapril, 9.2; MI-losartan, 8.8 mm Hg.mL-1.min-1.g-1, all P < .05 versus MI-placebo). Interstitial fibrosis determined from perfusion-fixed hearts was increased in infarcted rats but reduced by both enalapril and losartan. Myocardial capillary density improved with enalapril and losartan. In separate groups treated as above, plasma and tissue ACE activity was determined and demonstrated significantly higher ACE activity in noninfarcted LV tissue of MI-placebo rats compared with sham (0.64 vs 0.27 nmol.mg protein-1.min-1, P < .05). Enalapril and losartan reduced LV ACE activity (0.39 and 0.29 nmol.mg protein-1.min-1, P < .05 versus MI-placebo). CONCLUSIONS: The present study demonstrates that both chronic ACE inhibition and AT1 receptor blockade (1) reduces cardiac hypertrophy, (2) restores minimal coronary vascular resistance in postinfarction reactive hypertrophy, and (3) attenuates the development of myocardial interstitial fibrosis in the noninfarcted LV. These results suggest that inhibition of generation of angiotensin II and AT1 receptor blockade are equally effective in preventing important features of ventricular remodeling after myocardial infarction.

Angiotensin II↗
PubMed1994

Survival after myocardial infarction in the rat. Role of tissue angiotensin-converting enzyme inhibition.

BACKGROUND: Chronic treatment with high doses of angiotensin-converting enzyme (ACE) inhibitors prolongs survival after myocardial infarction. Since the plasma renin-angiotensin system (RAS) is not consistently activated in the chronic phase after myocardial infarction, the beneficial effects of ACE inhibition have been attributed, in part, to inhibition of an activated tissue RAS. However, a relation between tissue ACE inhibition and long-term efficacy (ie, concerning left ventricular [LV] hypertrophy and survival) has not been established. The present study was designed to evaluate the impact of low-dose ACE inhibition (predominant inhibition of plasma ACE) and high-dose ACE inhibition associated with substantial tissue ACE inhibition) on reversal of LV hypertrophy and 1-year mortality after myocardial infarction in the rat. METHODS AND RESULTS: Infarcted rats were randomized to placebo, low-dose lisinopril, or high-dose lisinopril (each, n = 80) and compared with sham-operated animals (n = 40). In a separate group of animals, tissue ACE activity was determined after 6 weeks of therapy, demonstrating that both regimens were effective with regard to both plasma and pulmonary ACE inhibition; however, only high-dose lisinopril inhibited renal ACE. Neither dose affected LV ACE activity and ACE mRNA levels as determined by competitive polymerase chain reaction, whereas LV ANF mRNA levels were significantly reduced by high-dose lisinopril. High-dose lisinopril reduced arterial blood pressure and normalized right ventricular and LV weight and resulted in a substantial reduction of 1-year mortality, whereas the low dose did not (1 year mortality: placebo, 56.3%; low dose, 53.3%; high dose, 22.9%, P < .0001 versus low dose and versus placebo). CONCLUSIONS: Hemodynamically effective ACE inhibition is required for reduction of LV hypertrophy and long-term mortality after myocardial infarction in the rat. Sustained inhibition of renal ACE during long-term therapy may contribute to the beneficial effect of high-dose lisinopril. Low-dose lisinopril, although exerting sustained inhibition of the plasma ACE, does not improve survival after myocardial infarction.

Animals↗
PubMed1994

Relation between myocardial function and expression of sarcoplasmic reticulum Ca(2+)-ATPase in failing and nonfailing human myocardium.

Expression of sarcoplasmic reticulum (SR) Ca(2+)-ATPase was shown to be reduced in failing human myocardium. The functional relevance of this finding, however, is not known. We investigated the relation between myocardial function and protein levels of SR Ca(2+)-ATPase in nonfailing human myocardium (8 muscle strips from 4 hearts) and in myocardium from end-stage failing hearts with dilated (10 muscle strips from 9 hearts) or ischemic (7 muscle strips from 5 hearts) cardiomyopathy. Myocardial function was evaluated by the force-frequency relation in isometrically contracting muscle strip preparations (37 degrees C, 30 to 180 min-1). In nonfailing myocardium, twitch tension rose with increasing rates of stimulation and was 76% higher at 120 min-1 compared with 30 min-1 (P < .02). In failing myocardium, there was no significant increase in average tension at stimulation rates above 30 min-1. At 120 min-1, twitch tension was decreased by 59% (P < .05) in dilated cardiomyopathy and 76% (P < .05) in ischemic cardiomyopathy compared with nonfailing myocardium. Protein levels of SR Ca(2+)-ATPase, normalized per total protein or per myosin, were reduced by 36% (P < .02) or 32% (P < .05), respectively, in failing compared with nonfailing myocardium. SR Ca(2+)-ATPase protein levels were closely related to SR Ca2+ uptake, measured in homogenates from the same hearts (r = .70, n = 16, and P < .005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Gene expression of the cardiac Na(+)-Ca2+ exchanger in end-stage human heart failure.

The regulation of cytosolic Ca2+ concentration during excitation-contraction coupling is altered in the failing human heart. Previous studies have focused on disturbances in Ca2+ release and reuptake from the sarcoplasmic reticulum (SR), whereas functional studies of the cardiac Na(+)-Ca2+ exchanger, another important determinant of myocyte homeostasis, are lacking for the failing human heart. Using a cardiac Na(+)-Ca2+ exchanger cDNA recently cloned from a guinea pig cDNA library, we investigated the gene expression of the cardiac Na(+)-Ca2+ exchanger in relation to the SR Ca(2+)-ATPase. Expression of both genes was quantified in left ventricular myocardium from 24 failing human cardiac explants and 7 control heart samples in relation to beta-myosin heavy chain mRNA by slot blot analysis. Compared with patients with nonfailing hearts, patients with dilated cardiomyopathy (DCM, n = 13) showed a 55% increase in Na(+)-Ca2+ exchanger mRNA levels (P < .05 versus control value) and a 41% increase in patients with coronary artery disease (CAD, n = 11). In the same hearts, SR Ca(2+)-ATPase mRNA levels were decreased by 50% in DCM and by 45% in CAD (P < .05 for both versus control value). There was a positive correlation between Na(+)-Ca2+ exchanger and SR Ca(2+)-ATPase mRNA levels both in normal and failing human hearts, albeit with different slopes and intercepts of the regression line. The Na(+)-Ca2+ exchanger protein levels as assessed by Western blot analysis and normalized to beta-myosin heavy chain protein were increased in DCM and CAD (P < .05 and P < .01 versus control value, respectively), whereas SR Ca(2+)-ATPase protein levels were reduced (P < .05 for both groups versus control values). Thus, the Na(+)-Ca2+ exchanger gene expression is enhanced in failing human hearts and may, in part, compensate for the depressed SR function with regard to diastolic Ca2+ removal.

Adult↗
PubMed1994

Increased angiotensin-I converting enzyme gene expression in the failing human heart. Quantification by competitive RNA polymerase chain reaction.

Local activation of the components of the renin angiotensin system in the heart is regarded as an important modulator of cardiac phenotype and function; however, little is known about their presence, regulation, and potential activation in the human heart. To investigate the gene expression of major angiotensin-II-forming enzymes in left ventricles of normal (n = 9) and failing human hearts (n = 20), we established a competitive RNA-polymerase chain reaction (PCR) for mRNA quantification of angiotensin-I converting enzyme (ACE) and human heart chymase. For each gene, competitor RNA targets with small internal deletions were used as internal standards to quantify the original number of transcripts and to control reverse transcription and PCR. In PCR, each target and the corresponding competitor were amplified by competing for the same primer oligonucleotides. The variability of ACE RNA-PCR was 11% indicating a high reproducibility of this method. In addition, ACE mRNA levels obtained by competitive RNA-PCR correlated favorably with traditional slot blot hybridization (r = 0.69, n = 10; P < 0.05). Compared with nonfailing hearts, the number of ACE transcripts referred to 100 ng of total RNA was increased threefold in patients with chronic heart failure (4.2 +/- 2.5 vs. 12.8 +/- 6 x 10(5); P < 0.0005). In contrast, no significant difference was found in chymase gene expression between normal and failing hearts. Thus, the expression of the cardiac ACE but not of human heart chymase is upregulated in failing human heart indicating an activation of the cardiac renin-angiotensin system in patients with advanced heart failure.

Adult↗
PubMed1994

Heart failure: an update on pathophysiology.

Myocardial hypertrophy is an established risk factor for cardiovascular morbidity and mortality. Beyond quantitative and mechanical aspects hypertrophy is associated with alterations in cardiac gene expression, resulting in a more fetal-like myocyte phenotype with a fragile Ca++ homeostasis. Depressed expression of sarcoplasmatic reticulum ATPase is the hallmark of this overload phenotype. Conversely, the gene expression and the activity of sodium calcium exchanger is up-regulated in endstage heart failure. Both alterations contribute to prolonged cytosolic Ca++ transients, disturbed relaxation and, probably, to electrophysiologic instability. Angiotensin II is a growth promoting agent and several lines of circumferential evidence suggest that the local formation of angiotensin II might contribute to the trophic response and phenotype shift in cardiac overload. The cardiac gene expression of angiotensin converting enzyme and angiotensinogen is increased early after cardiac overload and in patients with severe heart failure. Chronic ACE inhibition suppresses plasma and tissue ACE activity, reduces LV hypertrophy and improves long-term survival. The hallmark of the peripheral adaptation in chronic heart failure is systemic vasoconstriction, associated with neurohumoral activation. Several mechanisms are involved in the impaired peripheral perfusion, including increased sympathetic tone and increased vascular stiffness. Recently, data suggest an important role of the endothelium for perfusion of skeletal muscle in heart failure. Endothelium-dependent dilation of resistance vessels is blunted in patients with severe chronic heart failure. Conceivably, this abnormality may be involved in the impaired reactive hyperemia in patients with chronic heart failure. Moreover, alterations of skeletal muscle emerge in chronic heart failure contributing to reduced exercise performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1994

Unusual forms of ischemic heart disease.

Unusual forms and causes of ischemic heart disease include angina pectoris in the presence of normal coronary arteries (syndrome X), congenital coronary abnormalities, vasculitic disorders, and graft atherosclerosis after cardiac transplantation. There is now evidence that endothelial dysfunction of coronary resistance vessels can account for abnormalities of the coronary microvasculature and possibly, myocardial ischemia and chest pain. The incidence of syndrome X appears to be higher in women, particularly those who have undergone hysterectomy. An intriguing hypothesis is that low estrogen levels may be associated with reduced expression of nitric oxide (reflecting endothelial dysfunction). The presence of coronary abnormalities in the young should not be underestimated. Syncope and arrhythmias are observed frequently in this patient population and warrant vigorous exploration. Worldwide, cardiac transplantation is now carried out in approximately 4500 patients yearly, with excellent (80% to 90%) 1-year survival due to improved immunosuppression. However, accelerated atherosclerosis develops rapidly postoperatively and is the main cause of late death. The link between cellular rejection of the myocardium and transplant coronary artery disease is not clear. The process of transplant coronary artery disease is believed to be due to chronic immune injury followed by intimal smooth-muscle proliferation and lipid deposition in the vascular wall. By the time it is detected by coronary angiography, the disease is far advanced and not susceptible to routine revascularization procedures. A prospective, randomized study of diltiazem versus no calcium blocker started early after transplantation has documented highly significant reductions in transplant atherosclerosis as measured by lumen narrowing, clinical events, and rates of retransplantation or death due to the process.(ABSTRACT TRUNCATED AT 250 WORDS)

Death, Sudden, Cardiac↗
PubMed1994

Endothelial dysfunction in chronic heart failure. Experimental and clinical studies.

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)

Arginine↗