Basal nitric oxide production is impaired in offspring of patients with essential hypertension

1999 ◽  
Vol 97 (2) ◽  
pp. 141-147 ◽  
Author(s):  
A. S. McALLISTER ◽  
A. B. ATKINSON ◽  
G. D. JOHNSTON ◽  
D.R. HADDEN ◽  
P. M. BELL ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Essential Hypertension ◽  
Endothelial Dysfunction ◽  
Sodium Nitroprusside ◽  
Forearm Blood Flow ◽  
Competitive Inhibitor ◽  
Venous Occlusion ◽  
Limited Data ◽  
Vasoconstrictor Response ◽  
Normotensive Subjects

There is considerable evidence that endothelium-dependent nitric oxide (NO)-mediated vasodilatation in response to acetylcholine is impaired in essential hypertension, whereas the endothelium-independent response to sodium nitroprusside is normal. More limited data have suggested that there is also reduced vasoconstriction in response to NG-monomethyl-⌊-arginine (⌊-NMMA), a competitive inhibitor of basal NO release. As it is not known whether endothelial dysfunction in hypertension, if indeed present, is a cause or consequence of the condition, we have studied the normotensive offspring of parents with essential hypertension. Both basal and stimulated vascular responses were examined in 12 normotensive offspring [mean age (°S.E.M.) 26.1°1.4 years] of parents with essential hypertension and compared with those in 12 age-matched offspring (mean age 25.6°1.1 years) of normotensive subjects. Forearm blood flow was measured simultaneously in both arms by venous occlusion plethysmography, both at baseline and during intra-arterial brachial infusion of increasing doses of acetylcholine, sodium nitroprusside, noradrenaline and ⌊-NMMA. There were no significant differences between the groups in the responses to acetylcholine, sodium nitroprusside or noradrenaline. In contrast, the vasoconstrictor response to l-NMMA was significantly blunted in the offspring of hypertensive parents compared with that in the offspring of normotensive parents (P = 0.005). Thus endothelial dysfunction, as demonstrated by impaired basal production of NO, is present in subjects at high risk of essential hypertension, and does not occur simply as a consequence of the condition.

Abstract 403: Autonomic Blockade Improves “Endothelial Dysfunction” in Obesity-Associated Hypertensive Human Subjects

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Alfredo Gamboa ◽  
Rocio A Figueroa ◽  
Luis E Okamoto ◽  
Andre Diedrich ◽  
Italo Biaggioni
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Forearm Blood Flow ◽  
Human Subjects ◽  
Autonomic Activity ◽  
Sympathetic Activation ◽  
Autonomic Blockade ◽  
Obese Subjects ◽  
Normotensive Subjects ◽  
Obesity Hypertension

Nitric oxide (NO) deficiency (“endothelial dysfunction”) is a hallmark of obesity and is thought to contribute to hypertension. In a previous study, however, we did not find differences in NO function between hypertensive and normotensive subjects if autonomic activity was removed with ganglionic blockade. We hypothesized, therefore, that sympathetic activation, known to occur in obesity hypertension, contributes to NO mediated endothelial dysfunction. To test this hypothesis we determined NO-mediated vasodilation (increase in forearm blood flow, FBF, to intrabrachial acetylcholine, ACh) and endothelial independent vasodilation (intrabrachial sodium nitroprusside, SNP) in obese hypertensive subjects (30<BMI<40 kg/m2) during intact and during autonomic blockade (trimethaphan 4 mg/min IV infusion). Seven obese subjects (49±3.6 years, 34±1 kg/m2, 165/94 ± 7/6 mm Hg) were studied on two separate occasions, one month apart, randomly assigned. As anticipated, autonomic blockade increased basal FBF (from 3.9±0.7 to 5.2±1.2 ml/100mL/min, p=0.078). As expected, NO-mediated vasodilation was blunted on the intact day: FBF increased from 3.6±0.6 to 10.1±1.1 with SNP, but only from 3.7±0.4 to 7.2±0.8 ml/100mL/min with ACh, p=0.047. In contrast, during autonomic blockade, FBF responses to SNP and ACh were similar (from 5.2±0.9 to 12.5±0.9 and from 6.2±1.1 to 11.4±1.6 ml/100mL/min, respectively, p= 0.578, figure). Our results support the concept that sympathetic activation contributes to the impairment in NO-mediated vasodilation seen in obesity hypertension, and provides further rationale to explore it as a therapeutic target.

scholarly journals EvidenceIn VivoShowing Increase of Baseline Nitric Oxide Generation and Impairment of Endothelium-Dependent Vasodilation in Normotensive Patients on Chronic Hemodialysis

2000 ◽  
Vol 11 (9) ◽  
pp. 1726-1734 ◽  
Author(s):  
JENS PASSAUER ◽  
ECKHART BÜSSEMAKER ◽  
URSULA RANGE ◽  
MARIA PLUG ◽  
PETER GROSS
Keyword(s):  
Nitric Oxide ◽  
Vascular Tone ◽  
Forearm Blood Flow ◽  
Matched Control ◽  
Venous Occlusion ◽  
Chronic Hemodialysis ◽  
Invasive Technique ◽  
Vascular Effects ◽  
Control Subjects ◽  
Pharmacologic Agents

Abstract.Cardiovascular mortality is excessive in hemodialyzed patients. Observations in atherosclerosis suggest that endothelial dysfunction and impaired nitric oxide (NO) may be involved. However, the relation of endothelial NO to its vascular effects has not been studied conclusively in uremia. Therefore, to study these questions an invasive technique was used in normotensive patients who were on hemodialysis (HD;n= 11) and in matched control subjects (n= 11). Pharmacologic agents were infused into the brachial artery to test the chain of events from NO generation to smooth muscle cell relaxation, measuring forearm blood flow by venous occlusion plethysmography. Glyceroltrinitrate (GTN 1:2.2 nmol/min; GTN 2:4.4; GTN 3:8.8), infused to establish the reaction of the vessel wall to defined doses of NO, caused a reduced response in HD patients (control subjects: 183 ± 20 [SEM], 246 ± 26, and 338 ± 29%; HD patients: 161 ± 7, 206 ± 12, and 262 ± 24%; baseline = 100% for each group,P= 0.032 by ANOVA). All subsequent data were corrected for this decreased response to defined doses of NO in HD patients. L-arginine (10 mg/min), given to exclude substrate deficiency of NO synthase (NOS), caused no significant changes (control subjects: 108 ± 4%; HD patients: 103 ± 4%;P= NS). Acetylcholine (ACH 1:55 nmol/min; ACH 2:110; ACH 3:220), infused to stimulate endothelial NOS, had a significantly reduced effect in HD patients (control subjects: 246 ± 32, 340 ± 40, and 465 ± 52%; HD patients: 251 ± 55, 244 ± 36, and 318 ± 50%;P= 0.002).N-monomethyl-L-arginine (LMA 1:1 μmol/min; LMA 2:2; LMA 3:4), given to block baseline NO generation, showed an enhanced response in HD patients (control subjects: 90 ± 2, 83 ± 2, and 74 ± 4%; HD patients: 84 ± 3, 73 ± 3, and 64 ± 4%;P= 0.037). Vascular response to three doses of norepinephrine (60, 120, and 240 pmol/min) was comparable in both groups, which indicated similar endothelium-independent vasoconstriction. In summary, in normotensive HD patients, (1) vasodilation to defined doses of exogenous NO was reduced, (2) there was no evidence of substrate deficiency of NOS, and (3) stimulation of NOS was impaired; however, (4) baseline NO generation was increased. It is concluded that in HD patients, the NO system has a reduced capacity to regulate vascular tone and this impairment is most significant under conditions of NOS stimulation.

Hypoxia inhibits nitric oxide synthesis in isolated rabbit lung

1997 ◽  
Vol 272 (6) ◽  
pp. L1167-L1173 ◽  
Author(s):  
S. P. Kantrow ◽  
Y. C. Huang ◽  
A. R. Whorton ◽  
E. N. Grayck ◽  
J. M. Knight ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Competitive Inhibitor ◽  
Oxidation Products ◽  
No Oxidation ◽  
Severe Hypoxia ◽  
No Production ◽  
Rabbit Lung ◽  
Vasoconstrictor Response ◽  
Hypoxic Vasoconstriction ◽  
Oxide Synthase

Nitric oxide (NO.) has been proposed to modulate hypoxic vasoconstriction in the lung. The activity of nitric oxide synthase (NOS) can be inhibited by hypoxia because molecular oxygen is a necessary substrate for the enzyme. On the basis of this mechanism, we hypothesized that NOS activity has a key role in regulation of pulmonary vascular tone during hypoxia. We measured oxidation products of NO. released into the vasculature of isolated buffer-perfused rabbit lung ventilated with normoxic (21% O2), moderately hypoxic (5% O2), or anoxic (0% O2) gas using two methods. Mean PO2 in perfusate exiting the lung was 25 Torr during anoxic ventilation and 47 Torr during moderately hypoxic ventilation. We found that the amount of the NO. oxidation product nitrite released into the perfusate was suppressed significantly during ventilation with anoxic but not moderately hypoxic gas. During normoxic ventilation, nitrite release was inhibited by pretreatment with NG-monomethyl-L-arginine, a competitive inhibitor of NOS. To confirm that changes in nitrite concentration reflected changes in NO. release into the perfusate, major oxidation products of NO. (NOx) were assayed using a method for reduction of these products to NO. by vanadium(III) Cl. Release of NOx into the perfusate was suppressed by severe hypoxia (anoxic ventilation), and this effect was reversed by normoxia. Pulmonary vasoconstriction was observed during severe but not moderate hypoxia and was related inversely to the rate of nitrite release. These observations provide evidence that decreased NO. production contributes to the pulmonary vasoconstrictor response during severe hypoxia.

Characterization of endothelium-derived hyperpolarizing factor in the human forearm microcirculation

2001 ◽  
Vol 280 (6) ◽  
pp. H2470-H2477 ◽  
Author(s):  
Julian P. J. Halcox ◽  
Suresh Narayanan ◽  
Laura Cramer-Joyce ◽  
Rita Mincemoyer ◽  
Arshed A. Quyyumi
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Sodium Nitroprusside ◽  
Forearm Blood Flow ◽  
Human Subjects ◽  
Epoxyeicosatrienoic Acid ◽  
Healthy Human ◽  
Human Forearm ◽  
Oxide Synthase ◽  
Cytochrome P 450

The identity of endothelium-dependent hyperpolarizing factor (EDHF) in the human circulation remains controversial. We investigated whether EDHF contributes to endothelium-dependent vasomotion in the forearm microvasculature by studying the effect of K+ and miconazole, an inhibitor of cytochrome P-450, on the response to bradykinin in healthy human subjects. Study drugs were infused intra-arterially, and forearm blood flow was measured using strain-gauge plethysmography. Infusion of KCl (0.33 mmol/min) into the brachial artery caused baseline vasodilation and inhibited the vasodilator response to bradykinin, but not to sodium nitroprusside. Thus the incremental vasodilation induced by bradykinin was reduced from 14.3 ± 2 to 7.1 ± 2 ml · min−1 · 100 g−1( P < 0.001) after KCl infusion. A similar inhibition of the bradykinin ( P = 0.014), but not the sodium nitroprusside (not significant), response was observed with KCl after the study was repeated during preconstriction with phenylephrine to restore resting blood flow to basal values after KCl. Miconazole (0.125 mg/min) did not inhibit endothelium-dependent or -independent responses to ACh and sodium nitroprusside, respectively. However, after inhibition of cyclooxygenase and nitric oxide synthase with aspirin and N G-monomethyl-l-arginine, the forearm blood flow response to bradykinin ( P = 0.003), but not to sodium nitroprusside (not significant), was significantly suppressed by miconazole. Thus nitric oxide- and prostaglandin-independent, bradykinin-mediated forearm vasodilation is suppressed by high intravascular K+ concentrations, indicating a contribution of EDHF. In the human forearm microvasculature, EDHF appears to be a cytochrome P-450 derivative, possibly an epoxyeicosatrienoic acid.

Role of Nitric Oxide towards Vasodilator Effects of Substance P and ATP in Human Forearm Vessels

1997 ◽  
Vol 92 (2) ◽  
pp. 123-131 ◽  
Author(s):  
Masanari Shiramoto ◽  
Tsutomu Imaizumi ◽  
Yoshitaka Hirooka ◽  
Toyonari Endo ◽  
Takashi Namba ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Substance P ◽  
Sodium Nitroprusside ◽  
Forearm Blood Flow ◽  
Dependent Manner ◽  
Human Forearm ◽  
Before And After ◽  
Dose Dependent

1. It has been shown in animals that substance P as well as acetylcholine releases endothelium-derived nitric oxide and evokes vasodilatation and that ATP-induced vasodilatation is partially mediated by nitric oxide. The aim of this study was to examine whether vasodilator effects of substance P and ATP are mediated by nitric oxide in humans. 2. In healthy volunteers (n = 35), we measured forearm blood flow by a strain-gauge plethysmograph while infusing graded doses of acetylcholine, substance P, ATP or sodium nitroprusside into the brachial artery before and after infusion of NG-monomethyl-l-arginine (4 or 8 μmol/min for 5 min). In addition, we measured forearm blood flow while infusing substance P before and during infusion of l-arginine (10 mg/min, simultaneously), or before and 1 h after oral administration of indomethacin (75 mg). 3. Acetylcholine, substance P, ATP or sodium nitroprusside increased forearm blood flow in a dose-dependent manner. NG-Monomethyl-l-arginine decreased basal forearm blood flow and inhibited acetylcholine-induced vasodilatation but did not affect substance P-, ATP-, or sodium nitroprusside-induced vasodilatation. Neither supplementation of l-arginine nor pretreatment with indomethacin affected substance P-induced vasodilatation. 4. Our results suggest that, in the human forearm vessels, substance P-induced vasodilatation may not be mediated by either nitric oxide or prostaglandins and that ATP-induced vasodilatation may also not be mediated by nitric oxide.

scholarly journals Agonist-dependent variablity of contributions of nitric oxide and prostaglandins in human skeletal muscle

2005 ◽  
Vol 98 (4) ◽  
pp. 1251-1257 ◽  
Author(s):  
William G. Schrage ◽  
Niki M. Dietz ◽  
John H. Eisenach ◽  
Michael J. Joyner
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Animal Studies ◽  
Forearm Blood Flow ◽  
Feedback Inhibition ◽  
Venous Occlusion ◽  
No Synthase ◽  
Human Forearm ◽  
Independent Mechanism ◽  
Treatment Order

The relative contributions of endothelium-dependent dilators [nitric oxide (NO), prostaglandins (PGs), and endothelium-derived hyperpolarizing factor (EDHF)] in human limbs are poorly understood. We tested the hypothesis that relative contributions of NO and PGs differ between endothelial agonists acetylcholine (ACh; 1, 2, and 4 μg·dl−1·min−1) and bradykinin (BK; 6.25, 25, and 50 ng·dl−1·min−1). We measured forearm blood flow (FBF) using venous occlusion plethysmography in 50 healthy volunteers (27 ± 1 yr) in response to brachial artery infusion of ACh or BK in the absence and presence of inhibitors of NO synthase [NOS; with NG-monomethyl-l-arginine (l-NMMA)] and cyclooxygenase (COX; with ketorolac). Furthermore, we tested the idea that the NOS + COX-independent dilation (in the presence of l-NMMA + ketorolac, presumably EDHF) could be inhibited by exogenous NO administration, as reported in animal studies. FBF increased ∼10-fold in the ACh control; l-NMMA reduced baseline FBF and ACh dilation, whereas addition of ketorolac had no further effect. Ketorolac alone did not alter ACh dilation, but addition of l-NMMA reduced ACh dilation significantly. For BK infusion, FBF increased ∼10-fold in the control condition; l-NMMA tended to reduce BK dilation ( P < 0.1), and addition of ketorolac significantly reduced BK dilation. Similar to ACh, ketorolac alone did not alter BK dilation, but addition of l-NMMA reduced BK dilation. To test the idea that NO can inhibit the NOS + COX-independent portion of dilation, we infused a dose of sodium nitroprusside (NO-clamp technique) during ACh or BK that restored the reduction in baseline blood flow due to l-NMMA. Regardless of treatment order, the NO clamp restored baseline FBF but did not reduce the NOS + COX-independent dilation to ACh or BK. We conclude that the contribution of NO and PGs differs between ACh and BK, with ACh being more dependent on NO and BK being mostly dependent on a NOS + COX-independent mechanism (EDHF) in healthy young adults. The NOS + COX-independent dilation does not appear sensitive to feedback inhibition from NO in the human forearm.

Four weeks of cycle training increases basal production of nitric oxide from the forearm

1997 ◽  
Vol 272 (3) ◽  
pp. H1070-H1077 ◽  
Author(s):  
B. A. Kingwell ◽  
B. Sherrard ◽  
G. L. Jennings ◽  
A. M. Dart
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Blood Flow ◽  
Sodium Nitroprusside ◽  
Forearm Blood Flow ◽  
Protective Effects ◽  
Nitric Oxide Synthase Inhibitor ◽  
Nitrite Production ◽  
Cycle Training ◽  
Nitrate And Nitrite

The purpose of this study was to determine whether nontrained vascular beds might contribute to the beneficial effects of exercise, including reduced blood pressure by enhanced nitric oxide production. Thirteen healthy, sedentary male volunteers performed 4 wk of normal sedentary activity and 4 wk of cycle training in a randomized order. At the end of each intervention, venous occlusion plethysmography was used to study the forearm blood flow responses to intra-arterial infusions of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA), acetylcholine, and sodium nitroprusside. Training increased the maximal work-load and maximal oxygen consumption, whereas intrabrachial blood pressure was reduced. L-NMMA caused a greater vasoconstriction after training (P = 0.004). Net nitrate and nitrite consumption by the forearm was less after training both before and after administration of L-NMMA (P = 0.04), consistent with increased nitrate and nitrite production from nitric oxide metabolism. There was no difference in the response to acetylcholine or sodium nitroprusside between the two states. Preliminary studies showed an increase in forearm blood flow and blood viscosity after cycling, suggesting that elevated shear stress in this vascular bed may contribute to endothelial adaptation and the cardiovascular protective effects of exercise training.

scholarly journals Increased Blood Pressure Causes Lymphatic Endothelial Dysfunction via Oxidative Stress in Spontaneously Hypertensive Rats

Hypertension ◽  
2020 ◽  
Vol 76 (2) ◽  
pp. 598-606
Author(s):  
Masashi Mukohda ◽  
Risuke Mizuno ◽  
Hiroshi Ozaki
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
Nadph Oxidase ◽  
Sodium Nitroprusside ◽  
P38 Mapk ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

The lymphatic system is involved in the pathogenesis of edema, inflammation, and cancer metastasis. Because lymph vessels control fluid electrolytes and volume balance, changes in lymphatic activity can be expected to alter systemic blood pressure. This study examined possible changes in lymphatic contractile properties in spontaneously hypertensive rats (SHR). Thoracic ducts isolated from 10- to 12-week-old SHR exhibited either decreased acetylcholine-induced endothelium-dependent relaxation or sodium nitroprusside-induced endothelium-independent relaxation compared with age-matched Wister-Kyoto rats. The impairment in acetylcholine responsiveness was more pronounced than sodium nitroprusside responsiveness. N-Nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor blunted acetylcholine-induced relaxation in Wister-Kyoto rats, indicating an involvement of endothelial nitric oxide production. Endothelial dysfunction in lymph vessels of SHR was attenuated by tempol (a superoxide dismutase mimetic), apocynin, or VAS-2870 (NADPH oxidase inhibitors). Consistent with these observations, nitrotyrosine levels were significantly elevated in SHR, indicative of increased oxidative stress. In addition, protein expression of NADPH oxidase 2 and phosphorylation of p47 phox (Ser345) were significantly increased in SHR. Further, SB203580 (a p38 MAPK inhibitor) restored the acetylcholine-induced relaxation in SHR. It is notable that 4-week-old SHR, which exhibited normal blood pressure, did not show any decreased activity of acetylcholine- or sodium nitroprusside-induced relaxation. Additionally, antihypertensive treatment of 4-week-old SHR with hydrochlorothiazide and reserpine or hydrochlorothiazide and hydralazine for 6 weeks completely restored lymphatic endothelial dysfunction. We conclude that contractile activity of lymphatic vessels is functionally impaired with the development of increasing blood pressure, which is mediated through increased oxidative stress via the p38 MAPK/NADPH oxidase 2 pathway.

L-Arginine protects from ischemia-reperfusion-induced endothelial dysfunction in humans in vivo

2003 ◽  
Vol 95 (6) ◽  
pp. 2218-2222 ◽  
Author(s):  
John Pernow ◽  
Felix Böhm ◽  
Emma Beltran ◽  
Adrian Gonon
Keyword(s):  
Blood Flow ◽  
Endothelial Dysfunction ◽  
Reperfusion Injury ◽  
Forearm Blood Flow ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Venous Occlusion ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

It has been shown that nitric oxide (NO) protects from myocardial ischemia-reperfusion injury in animal models. The present study investigated whether administration of the NO substrate l-arginine protects against ischemia-reperfusion-induced endothelial dysfunction in humans. Forearm blood flow was measured with venous occlusion plethysmography in 16 healthy male subjects who were investigated on two occasions. Forearm ischemia was induced for 20 min followed by 60-min reperfusion. With the use of a crossover protocol, the subject received a 15-min intrabrachial artery infusion of l-arginine (20 mg/min) and vehicle (saline, n = 12 or d-arginine, n = 4) starting at 15 min of ischemia on two separate occasions. Compared with preischemia, endothelium-dependent increase in forearm blood flow induced by intra-arterial acetylcholine (3–30 μg/min) was significantly impaired at 15 and 30 min of reperfusion when the subjects received saline ( P < 0.001). When the subjects received l-arginine, the acetylcholine-induced increase in forearm blood flow was not significantly affected by ischemia-reperfusion. The recovery of endothelium-dependent vasodilatation at 15- and 30-min reperfusion was significantly greater after administration of l-arginine than after saline ( P < 0.05). d-Arginine did not affect the response to acetylcholine. Endothelium-independent vasodilatation to nitroprusside was not affected during reperfusion. These results demonstrate that the NO substrate l-arginine significantly attenuates ischemia-reperfusion-induced endothelial dysfunction in humans in vivo. This suggests that l-arginine may be useful as a therapeutic agent in the treatment of ischemia-reperfusion injury in humans.

Nitric oxide and asymmetric dimethylarginine (ADMA) in malignancy associated thrombosis and their modulation by anticoagulants

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10573-10573
Author(s):  
J. Fareed ◽  
D. A. Hoppensteadt ◽  
M. Demir ◽  
O. Iqbal ◽  
W. Jeske ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Cancer Patients ◽  
Asymmetric Dimethylarginine ◽  
Oral Anticoagulants ◽  
Treated Group ◽  
Competitive Inhibitor ◽  
No Production ◽  
Open Label ◽  
Stage Renal Disease

10573 Background: Cancer associated thrombotic complications are primarily due to endothelial dysfunction and upregulation of inflammatory processes. Nitric oxide (NO) represents one of the major endothelial derived vasoactive mediators. Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of NO synthase which inhibits NO production at pathophysiologic levels. Plasma ADMA levels are upregulated in atherosclerosis, hypertension, end stage renal disease, chronic heart failure and microangiopathy. Methods: To test the hypothesis that endothelial dysfunction in cancer patients may result in increased ADMA levels, plasma samples were retrospectively analyzed from an open label, multidose, active comparator designed study in which all patients (n = 110) were initially treated with low molecular weight heparin, enoxaparin (E) at 1–1.5 mg/kg sc for 5 days and further subdivided into group E which continued to receive E and warfarin (W) group which was given oral anticoagulants for a period of up to 12 weeks. Baseline blood samples (BL), 5 days post E (IPE) and 4–6 week samples from the E and W were analyzed for ADMA and NO levels by ELISA methods. Results: Both the ADMA and NO levels were markedly elevated in cancer patients. The E treated group showed a marked decrease in the ADMA levels which persisted throughout the treatment period. However, in the W converted group the ADMA levels rebounded to an increased level indicating that E differentially regulated ADMA in these patients. The down regulation pattern of NO was similar for both E and W. Conclusions: These results suggest that patients with cancer and thrombosis exhibit simultaneous upregulation of ADMA and NO. While E and W show a differential regulation of ADMA both result in downregulation of NO. The fact that E regulates ADMA is highly suggestive of its role in iNOS regulation which may be involved in the inflammatory response in cancer patients. [Table: see text] No significant financial relationships to disclose.

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