scholarly journals Airway and alveolar nitric oxide production, lung function, and pulmonary blood flow in sickle cell disease

2015 ◽  
Vol 79 (2) ◽  
pp. 313-317 ◽  
Author(s):  
Alan Lunt ◽  
Na'eem Ahmed ◽  
Gerrard F. Rafferty ◽  
Moira Dick ◽  
David Rees ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Sickle Cell Disease ◽  
Lung Function ◽  
Sickle Cell ◽  
Pulmonary Blood Flow ◽  
Nitric Oxide Production ◽  
Cell Disease ◽  
Oxide Production

Hydroxyurea and Arginine Therapy: Impact on Nitric Oxide Production in Sickle Cell Disease

2003 ◽  
Vol 25 (8) ◽  
pp. 629-634 ◽  
Author(s):  
Claudia R. Morris ◽  
Elliott P. Vichinsky ◽  
Jane van Warmerdam ◽  
Lorenzo Machado ◽  
Diane Kepka-Lenhart ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Nitric Oxide Production ◽  
Cell Disease ◽  
Oxide Production

scholarly journals L-Arginine Therapy Paradoxically Decreases Nitric Oxide Production in Patients with Sickle Cell Disease

1999 ◽  
Vol 45 (4, Part 2 of 2) ◽  
pp. 150A-150A
Author(s):  
Claudia R Morris ◽  
Frans Kuypers ◽  
Sandra Larkin ◽  
Nancy Kennedy ◽  
Julie Simon ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Nitric Oxide Production ◽  
Cell Disease ◽  
Oxide Production

Arginine therapy: a novel strategy to induce nitric oxide production in sickle cell disease. SHORT REPORT

2000 ◽  
Vol 111 (2) ◽  
pp. 498-500 ◽  
Author(s):  
Claudia R. Morris ◽  
Frans A. Kuypers ◽  
Sandra Larkin ◽  
Nancy Sweeters ◽  
Julie Simon ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Short Report ◽  
Nitric Oxide Production ◽  
Cell Disease ◽  
Oxide Production ◽  
Novel Strategy

scholarly journals Arginine therapy: a novel strategy to induce nitric oxide production in sickle cell disease

2000 ◽  
Vol 111 (2) ◽  
pp. 498-500 ◽  
Author(s):  
Claudia R. Morris ◽  
Frans A. Kuypers ◽  
Sandra Larkin ◽  
Nancy Sweeters ◽  
Julie Simon ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Nitric Oxide Production ◽  
Cell Disease ◽  
Oxide Production ◽  
Novel Strategy

Decrease in lung nitric oxide production after peritonitis in mice with sickle cell disease*

2007 ◽  
Vol 35 (2) ◽  
pp. 502-509 ◽  
Author(s):  
Pablo Bartolucci ◽  
Minh-Triet Ngo ◽  
Yves Beuzard ◽  
Frédéric Galactéros ◽  
Guitanouch Saber ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Nitric Oxide Production ◽  
Cell Disease ◽  
Oxide Production

scholarly journals Mechanisms of Stroke in Sickle Cell Disease: Sickle Erythrocytes Decrease Cerebral Blood Flow in Rats After Nitric Oxide Synthase Inhibition

Blood ◽  
1997 ◽  
Vol 89 (12) ◽  
pp. 4591-4599 ◽  
Author(s):  
James A. French ◽  
Dermot Kenny ◽  
J. Paul Scott ◽  
Raymond G. Hoffmann ◽  
James D. Wood ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Vascular Endothelium ◽  
Cell Disease ◽  
Cerebral Microvessels ◽  
Doppler Flowmetry ◽  
Cranial Window

Abstract The etiology of stroke in sickle cell disease is unclear, but may involve abnormal red blood cell (RBC) adhesion to the vascular endothelium and altered vasomotor tone regulation. Therefore, we examined both the adhesion of sickle (SS)-RBCs to cerebral microvessels and the effect of SS-RBCs on cerebral blood flow when the nitric oxide (NO) pathway was inhibited. The effect of SS-RBCs was studied in the rat cerebral microcirculation using either a cranial window for direct visualization of infused RBCs or laser Doppler flowmetry (LDF ) to measure RBC flow. When fluorescently labeled human RBCs were infused into rats, SS-RBCs had increased adhesion to rat cerebral microvessels compared with control AA-RBCs (P = .01). Next, washed SS-RBCs or AA-RBCs were infused into rats prepared with LDF probes after pretreatment (40 mg/kg intravenously) with the NO synthase inhibitor, N-ω-nitro-L-arginine methyl ester (L-NAME), or the control isomer, D-NAME. In 9 rats treated with systemic L-NAME and SS-RBCs, 5 of 9 experienced a significant decrease in LDF and died within 30 minutes after the RBC infusion (P = .0012). In contrast, all control groups completed the experiment with stable LDF and hemodynamics. Four rats received a localized superfusion of L-NAME (1 mmol/L) through the cranial window followed by infusion of SS-RBCs. Total cessation of flow in all observed cerebral microvessels occurred in 3 of 4 rats within 15 minutes after infusion of SS-RBCs. We conclude that the NO pathway is critical in maintaining cerebral blood flow in the presence of SS-RBCs in this rat model. In addition, the enhanced adhesion of SS-RBCs to rat brain microvessels may contribute to cerebral vaso-occlusion either directly, by disrupting blood flow, or indirectly, by disturbing the vascular endothelium.

The Arginine-to-Ornithine Ratio: Biomarker of Arginase Activity and Predictor of Mortality in Sickle Cell Disease.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 237-237 ◽  
Author(s):  
Claudia R. Morris ◽  
Gregory Kato ◽  
Mirjana Poljakovic ◽  
William C. Blackwelder ◽  
Stan Hazen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Endothelial Dysfunction ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Risk Ratio ◽  
Arginase Activity ◽  
Nitric Oxide Production ◽  
Cell Disease ◽  
Arginine Metabolism

Abstract Sickle cell disease (SCD) is characterized by a state of nitric oxide resistance and limited bioavailability of L-arginine, the substrate for nitric oxide synthesis. While nitric oxide resistance occurs secondary to inactivation of nitric oxide by plasma hemoglobin released during intravascular hemolysis and by reactive oxygen species, mechanisms that limit L-arginine are not known. We hypothesized that increased arginase activity in patients with SCD would shift arginine metabolism away from nitric oxide production and towards ornithine metabolism, contributing to endothelial dysfunction and the development of pulmonary hypertension. Furthermore, since arginine and ornithine compete for the same transport system for cellular uptake, a decrease in the Arginine-to-Ornithine ratio resulting from increased arginase activity could also impair arginine bioavailability for nitric oxide production. Our goal was to evaluate associations between plasma arginase, arginine metabolism and pulmonary hypertension and prospective mortality in SCD. Plasma and erythrocyte arginase activity and amino acid levels were determined for patients with SCD and compared to ethnically matched control subjects. A diagnosis of pulmonary hypertension by Doppler-echocardiogram and prospective mortality were determined over 30 months of sequential patient enrollment. Plasma arginase activity was significantly elevated in patients with SCD compared to controls (2.2±2, n=140 vs. 0.4±2 μmol/ml/hr, n=45, p=0.007), trending higher in subjects with pulmonary hypertension. Plasma arginase activity correlated with the Arginine-to-Ornithine ratio (r=−0.33, p=0.0004), and lower ratios were associated with greater severity of pulmonary hypertension (1.1±0.4 vs. 0.8±0.4 vs. 0.6±0.3, controls vs. SCD without pulmonary hypertension vs. SCD with pulmonary hypertension, respectively, p=0.01) and independently associated with mortality (0.7±0.4 vs. 0.5±0.2, alive vs. dead, p=0.003; Risk Ratio = 4.9 [CI: 1.4, 17.1], p=0.002, for a low Arginine-to-Ornithine ratio; 13 deaths total). The mortality risk ratio increased to 7.0 ([CI: 1.6, 31.6], p=0.01), when the Arginine-to-Ornithine ratio was adjusted for creatinine, likely reflecting the impact of renal disease. Plasma arginase activity correlated with markers of increased hemolytic rate, including LDH (r=0.44, p<0.001), AST (r=0.39, p<0.002), reticulocyte count (r=0.25, p<0.001), and Hct (r= −0.25, p<0.001), and was higher in erythrocytes of SCD patients compared to controls (37.7±2.9, n=16 vs 23.5±1.7 nmol/mg/min, n=45, p<0.0001), consistent with hemolytic release of erythrocyte arginase. These data support a novel mechanism of disease whereby hemolysis not only liberates vasoactive hemoglobin but also releases erythrocyte arginase, which contributes to impaired nitric oxide bioavailability, endothelial dysfunction, pulmonary hypertension and death. The Arginine-to-Ornithine ratio, a reflection of arginase activity, may represent a useful biomarker of disease severity and risk of death in patients with SCD.

Sodium Nitrite Increases Regional Blood Flow in Patients with Sickle Cell Disease.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2328-2328
Author(s):  
A. Kyle Mack ◽  
Roberto F. Machado ◽  
Vandana Sachdev ◽  
Mark T. Gladwin ◽  
Gregory J. Kato
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Forearm Blood Flow ◽  
Regional Blood Flow ◽  
Cell Disease ◽  
No Donor ◽  
No Donors ◽  
Before And After

Abstract Patients with sickle cell disease have decreased nitric oxide bioavailability, and studies from several groups have confirmed a blunted response to various NO donors in humans and mice with sickle cell disease. Recently published studies show that nitrite induces vasodilation in humans, apparently mediated by conversion of nitrite to NO. This study is designed to determine the potential therapeutic effect of intra-arterial nitrite infusion to restore nitric oxide dependent blood flow in the forearms of patients with sickle cell disease. Venous occlusion strain gauge plethysmography is used to measure the change of forearm blood flow in patients with sickle cell disease, before and after sequential brachial artery infusions of increasing doses of sodium nitrite. In addition, NO responsiveness before and after nitrite infusion is measured by test doses of the NO donor sodium nitroprusside (SNP). Six patients have completed the study and enrollment is continuing. These data indicate that nitrite promotes regional blood flow in patients with sickle cell disease, albeit with a blunted response compared to our healthy control subjects, in whom we previously have found increased blood flow up to 187% with comparable dosing. The significant but blunted response is consistent with the state of nitric oxide resistance to NO donors that has been seen by several groups in patients and mice with SCD. Additionally, we find in these patients that nitrite partially restores SNP responsiveness, with baseline maximal SNP responses more than doubling on average following nitrite infusion, although this finding is preliminary. No adverse effects of nitrite were seen in these six patients. Our early results support a role for nitrite as an NO donor effective in restoring NO-dependent blood flow in patients with sickle cell disease. Additional translational studies are warranted to evaluate the therapeutic effects of systemic nitrite dosing. Table 1. Forearm Blood Flow Response to Nitrite Infusion Nitrite Dose (micromole/min) Sickle Cell Disease Historical Controls P< .0001 (ANOVA) 0.4 5 +/−7.2% N=6 22 +/−3.2% N=10 4 15 +/− 11% N=6 Not infused 40 49 +/− 8.9% N=6 187 +/− 16%N=18 Table 2. Nitrite Effect on Nitroprusside Responsiveness SNP Dose (micrograms/min) Pre-Nitrite Post-Nitrite P= .02 (RM-ANOVA) N=6 0.8 +21 +/− 5.6% +33 +/− 8.3% 1.6 +15 +/− 5.9% +62 +/− 15.1% 3.2 +29 +/− 6.3% +67 +/− 11.5%

scholarly journals Alterations in Nitric Oxide Production in 8-Week-Old Lambs with Increased Pulmonary Blood Flow

2002 ◽  
Vol 52 (2) ◽  
pp. 233-244 ◽  
Author(s):  
Stephen M Black ◽  
Janine M Bekker ◽  
D Michael McMullan ◽  
Andrew J Parry ◽  
Boaz Ovadia ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Pulmonary Blood Flow ◽  
Nitric Oxide Production ◽  
Oxide Production
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