Mark T. Gladwin

Role of the anion nitrite in ischemia-reperfusion cytoprotection and therapeutics (2007)

Dezfulian, Cameron, Raat, Nicolaas, Shiva, Sruti, Gladwin, Mark T.

The anion nitrite (NO2−) constitutes a biochemical reservoir for nitric oxide (NO). Nitrite reduction to NO may be catalyzed by hemoglobin, myoglobin or other metal-containing enzymes and occurs at...

Role of circulating nitrite and S-nitrosohemoglobin in the regulation of regional blood flow in humans

Gladwin, Mark T., Shelhamer, James H., Schechter, Alan N., Pease-Fye, Margaret E., Waclawiw, Myron A., Panza, Julio A., ...

To determine the relative contributions of endothelial-derived nitric oxide (NO) vs. intravascular nitrogen oxide species in the regulation of human blood flow, we simultaneously measured forearm...

Relative role of heme nitrosylation and β-cysteine 93 nitrosation in the transport and metabolism of nitric oxide by hemoglobin in the human circulation

Gladwin, Mark T., Ognibene, Frederick P., Pannell, Lewis K., Nichols, James S., Pease-Fye, Margaret E., Shelhamer, James H., ...

To quantify the reactions of nitric oxide (NO) with hemoglobin under physiological conditions and to test models of NO transport on hemoglobin, we have developed an assay to measure NO–hemoglobin...

Oxygen radical inhibition of nitric oxide-dependent vascular function in sickle cell disease

Aslan, Mutay, Ryan, Thomas M., Adler, Brian, Townes, Tim M., Parks, Dale A., Thompson, J. Anthony, ...

Plasma xanthine oxidase (XO) activity was defined as a source of enhanced vascular superoxide (O\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts}...

Hydroxyurea induces fetal hemoglobin by the nitric oxide–dependent activation of soluble guanylyl cyclase

Cokic, Vladan P., Smith, Reginald D., Beleslin-Cokic, Bojana B., Njoroge, Joyce M., Miller, Jeffery L., Gladwin, Mark T., ...

Hydroxyurea treatment of patients with sickle-cell disease increases fetal hemoglobin (HbF), which reduces hemoglobin S polymerization and clinical complications. Despite its use in the treatment of...

Effects of inhaled nitric oxide on regional blood flow are consistent with intravascular nitric oxidedelivery

Cannon, Richard O., Schechter, Alan N., Panza, Julio A., Ognibene, Frederick P., Pease-Fye, Margaret E., Waclawiw, Myron A., ...

Nitric oxide (NO) may be stabilized by binding to hemoglobin, by nitrosating thiol-containing plasma molecules, or by conversion to nitrite, all reactions potentially preserving its bioactivity in...

Measurements of nitric oxide on the heme iron and β-93 thiol of human hemoglobin during cycles of oxygenation and deoxygenation

Xu, Xiuli, Cho, Man, Spencer, Netanya Y., Patel, Neil, Huang, Zhi, Shields, Howard, ...

Nitric oxide has been proposed to be transported by hemoglobin as a third respiratory gas and to elicit vasodilation by an oxygen-linked (allosteric) mechanism. For hemoglobin to transport nitric...

Haldane, hot dogs, halitosis, and hypoxic vasodilation: the emerging biology of the nitrite anion

Gladwin, Mark T.

While it has long been known that the reduction of nitrite to nitric oxide (NO) forms iron-nitrosyl-myoglobin and is the basis of meat curing, a greater biological activity of the nitrite anion has...

Inhaled nitric oxide augments nitric oxide transport on sickle cell hemoglobin without affecting oxygen affinity

Gladwin, Mark T., Schechter, Alan N., Shelhamer, James H., Pannell, Lewis K., Conway, Deirdre A., Hrinczenko, Borys W., ...

Nitric oxide (NO) inhalation has been reported to increase the oxygen affinity of sickle cell erythrocytes. Also, proposed allosteric mechanisms for hemoglobin, based on S-nitrosation of β-chain...

Biological activity of nitric oxide in the plasmatic compartment

Wang, Xunde, Tanus-Santos, Jose E., Reiter, Christopher D., Dejam, Andre, Shiva, Sruti, Smith, Reginald D., ...

There exist reaction products of nitric oxide (NO) with blood that conserve its bioactivity and transduce an endocrine vasomotor function under certain conditions. Although S-nitrosated albumin has...

Cytoprotective effects of nitrite during in vivo ischemia-reperfusion of the heart and liver

Duranski, Mark R., Greer, James J.M., Dejam, Andre, Jaganmohan, Sathya, Hogg, Neil, Langston, William, ...

Nitrite represents a circulating and tissue storage form of NO whose bioactivation is mediated by the enzymatic action of xanthine oxidoreductase, nonenzymatic disproportionation, and reduction by...

Enzymatic function of hemoglobin as a nitrite reductase that produces NO under allosteric control

Huang, Zhi, Shiva, Sruti, Kim-Shapiro, Daniel B., Patel, Rakesh P., Ringwood, Lorna A., Irby, Cynthia E., ...

Hypoxic vasodilation is a fundamental, highly conserved physiological response that requires oxygen and/or pH sensing coupled to vasodilation. While this process was first characterized more than 80...

Hemolysis-associated endothelial dysfunction mediated by accelerated NO inactivation by decompartmentalized oxyhemoglobin

Minneci, Peter C., Deans, Katherine J., Zhi, Huang, Yuen, Peter S.T., Star, Robert A., Banks, Steven M., ...

During intravascular hemolysis in human disease, vasomotor tone and organ perfusion may be impaired by the increased reactivity of cell-free plasma hemoglobin (Hb) with NO. We experimentally produced...

Deconstructing endothelial dysfunction: soluble guanylyl cyclase oxidation and the NO resistance syndrome

Gladwin, Mark T.

In this issue of the JCI, Stasch and colleagues suggest that a novel drug, BAY 58-2667, potently activates a pool of oxidized and heme-free soluble guanylyl cyclase (sGC; see the related article...

Role of circulating nitrite and S-nitrosohemoglobin in the regulation of regional blood flow in humans

Gladwin, Mark T., Shelhamer, James H., Schechter, Alan N., Pease-Fye, Margaret E., Waclawiw, Myron A., Panza, Julio A., ...

To determine the relative contributions of endothelial-derived nitric oxide (NO) vs. intravascular nitrogen oxide species in the regulation of human blood flow, we simultaneously measured forearm...

Relative role of heme nitrosylation and β-cysteine 93 nitrosation in the transport and metabolism of nitric oxide by hemoglobin in the human circulation

Gladwin, Mark T., Ognibene, Frederick P., Pannell, Lewis K., Nichols, James S., Pease-Fye, Margaret E., Shelhamer, James H., ...

To quantify the reactions of nitric oxide (NO) with hemoglobin under physiological conditions and to test models of NO transport on hemoglobin, we have developed an assay to measure NO–hemoglobin...

Oxygen radical inhibition of nitric oxide-dependent vascular function in sickle cell disease

Aslan, Mutay, Ryan, Thomas M., Adler, Brian, Townes, Tim M., Parks, Dale A., Thompson, J. Anthony, ...

Plasma xanthine oxidase (XO) activity was defined as a source of enhanced vascular superoxide (O\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts}...

Hydroxyurea induces fetal hemoglobin by the nitric oxide–dependent activation of soluble guanylyl cyclase

Cokic, Vladan P., Smith, Reginald D., Beleslin-Cokic, Bojana B., Njoroge, Joyce M., Miller, Jeffery L., Gladwin, Mark T., ...

Hydroxyurea treatment of patients with sickle-cell disease increases fetal hemoglobin (HbF), which reduces hemoglobin S polymerization and clinical complications. Despite its use in the treatment of...

Effects of inhaled nitric oxide on regional blood flow are consistent with intravascular nitric oxidedelivery

Cannon, Richard O., Schechter, Alan N., Panza, Julio A., Ognibene, Frederick P., Pease-Fye, Margaret E., Waclawiw, Myron A., ...

Nitric oxide (NO) may be stabilized by binding to hemoglobin, by nitrosating thiol-containing plasma molecules, or by conversion to nitrite, all reactions potentially preserving its bioactivity in...

Measurements of nitric oxide on the heme iron and β-93 thiol of human hemoglobin during cycles of oxygenation and deoxygenation

Xu, Xiuli, Cho, Man, Spencer, Netanya Y., Patel, Neil, Huang, Zhi, Shields, Howard, ...

Nitric oxide has been proposed to be transported by hemoglobin as a third respiratory gas and to elicit vasodilation by an oxygen-linked (allosteric) mechanism. For hemoglobin to transport nitric...

Haldane, hot dogs, halitosis, and hypoxic vasodilation: the emerging biology of the nitrite anion

Gladwin, Mark T.

While it has long been known that the reduction of nitrite to nitric oxide (NO) forms iron-nitrosyl-myoglobin and is the basis of meat curing, a greater biological activity of the nitrite anion has...

Inhaled nitric oxide augments nitric oxide transport on sickle cell hemoglobin without affecting oxygen affinity

Gladwin, Mark T., Schechter, Alan N., Shelhamer, James H., Pannell, Lewis K., Conway, Deirdre A., Hrinczenko, Borys W., ...

Nitric oxide (NO) inhalation has been reported to increase the oxygen affinity of sickle cell erythrocytes. Also, proposed allosteric mechanisms for hemoglobin, based on S-nitrosation of β-chain...

Biological activity of nitric oxide in the plasmatic compartment

Wang, Xunde, Tanus-Santos, Jose E., Reiter, Christopher D., Dejam, Andre, Shiva, Sruti, Smith, Reginald D., ...

There exist reaction products of nitric oxide (NO) with blood that conserve its bioactivity and transduce an endocrine vasomotor function under certain conditions. Although S-nitrosated albumin has...

Cytoprotective effects of nitrite during in vivo ischemia-reperfusion of the heart and liver

Duranski, Mark R., Greer, James J.M., Dejam, Andre, Jaganmohan, Sathya, Hogg, Neil, Langston, William, ...

Nitrite represents a circulating and tissue storage form of NO whose bioactivation is mediated by the enzymatic action of xanthine oxidoreductase, nonenzymatic disproportionation, and reduction by...

Enzymatic function of hemoglobin as a nitrite reductase that produces NO under allosteric control

Huang, Zhi, Shiva, Sruti, Kim-Shapiro, Daniel B., Patel, Rakesh P., Ringwood, Lorna A., Irby, Cynthia E., ...

Hypoxic vasodilation is a fundamental, highly conserved physiological response that requires oxygen and/or pH sensing coupled to vasodilation. While this process was first characterized more than 80...

Hemolysis-associated endothelial dysfunction mediated by accelerated NO inactivation by decompartmentalized oxyhemoglobin

Minneci, Peter C., Deans, Katherine J., Zhi, Huang, Yuen, Peter S.T., Star, Robert A., Banks, Steven M., ...

During intravascular hemolysis in human disease, vasomotor tone and organ perfusion may be impaired by the increased reactivity of cell-free plasma hemoglobin (Hb) with NO. We experimentally produced...

Deconstructing endothelial dysfunction: soluble guanylyl cyclase oxidation and the NO resistance syndrome

Gladwin, Mark T.

In this issue of the JCI, Stasch and colleagues suggest that a novel drug, BAY 58-2667, potently activates a pool of oxidized and heme-free soluble guanylyl cyclase (sGC; see the related article...

Erythrocytes are the major intravascular storage sites of nitrite in human blood

Dejam, André, Hunter, Christian J., Pelletier, Mildred M., Hsu, Lewis L., Machado, Roberto F., Shiva, Sruti, ...

Plasma levels of nitrite ions have been used as an index of nitric oxide synthase (NOS) activity in vivo. Recent data suggest that nitrite is a potential intravascular repository for nitric oxide...

Hypoxia, red blood cells, and nitrite regulate NO-dependent hypoxic vasodilation

Crawford, Jack H., Isbell, T. Scott, Huang, Zhi, Shiva, Sruti, Chacko, Balu K., Schechter, Alan N., ...

Local vasodilation in response to hypoxia is a fundamental physiologic response ensuring oxygen delivery to tissues under metabolic stress. Recent studies identify a role for the red blood cell...

Lactate dehydrogenase as a biomarker of hemolysis-associated nitric oxide resistance, priapism, leg ulceration, pulmonary hypertension, and death in patients with sickle cell disease

Kato, Gregory J., McGowan, Vicki, Machado, Roberto F., Little, Jane A., Taylor, James, Morris, Claudia R., ...

Pulmonary hypertension is prevalent in adult patients with sickle cell disease and is strongly associated with early mortality and markers of hemolysis, in particular, serum lactate dehydrogenase...

Nitrite augments tolerance to ischemia/reperfusion injury via the modulation of mitochondrial electron transfer

Shiva, Sruti, Sack, Michael N., Greer, James J., Duranski, Mark, Ringwood, Lorna A., Burwell, Lindsay, ...

Nitrite (NO2−) is an intrinsic signaling molecule that is reduced to NO during ischemia and limits apoptosis and cytotoxicity at reperfusion in the mammalian heart, liver, and brain. Although the...

Hemolysis in sickle cell mice causes pulmonary hypertension due to global impairment in nitric oxide bioavailability

Hsu, Lewis L., Champion, Hunter C., Campbell-Lee, Sally A., Bivalacqua, Trinity J., Manci, Elizabeth A., Diwan, Bhalchandra A., ...

Pulmonary hypertension is a highly prevalent complication of sickle cell disease and is a strong risk factor for early mortality. However, the pathophysiologic mechanisms leading to pulmonary...

Hemodynamic and Functional Assessment of Patients with Sickle Cell Disease and Pulmonary Hypertension

Anthi, Anastasia, Machado, Roberto F., Jison, Maria L., Taveira-DaSilva, Angelo M., Rubin, Lewis J., Hunter, Lori, ...

Rationale: Although pulmonary hypertension (PH) is a common complication of sickle cell disease (SCD) associated with high mortality, there exist few data characterizing hemodynamics and...

Platelet activation in patients with sickle disease, hemolysis-associated pulmonary hypertension, and nitric oxide scavenging by cell-free hemoglobin

Villagra, José, Shiva, Sruti, Hunter, Lori A., Machado, Roberto F., Gladwin, Mark T., Kato, Gregory J.

Increased platelet activation is recognized in patients with sickle cell disease (SCD), but its pathogenesis and clinical relevance remain uncertain. Pulmonary arterial hypertension (PAH), an...

A network model to predict the risk of death in sickle cell disease

Sebastiani, Paola, Nolan, Vikki G., Baldwin, Clinton T., Abad-Grau, Maria M., Wang, Ling, Adewoye, Adeboye H., ...

Modeling the complexity of sickle cell disease pathophysiology and severity is difficult. Using data from 3380 patients accounting for all common genotypes of sickle cell disease, Bayesian network...

Nitrite reductase activity of myoglobin regulates respiration and cellular viability in myocardial ischemia-reperfusion injury

Hendgen-Cotta, Ulrike B., Merx, Marc W., Shiva, Sruti, Schmitz, Joel, Becher, Stefanie, Klare, Johann P., ...

The nitrite anion is reduced to nitric oxide (NO•) as oxygen tension decreases. Whereas this pathway modulates hypoxic NO• signaling and mitochondrial respiration and limits myocardial infarction...

Elevated tricuspid regurgitant jet velocity in children and adolescents with sickle cell disease: association with hemolysis and hemoglobin oxygen desaturation

Minniti, Caterina P., Sable, Craig, Campbell, Andrew, Rana, Sohail, Ensing, Gregory, Dham, Niti, ...

An elevated echocardiography-determined tricuspid regurgitant jet velocity predicts high systolic pulmonary artery pressure and early mortality in adults with sickle cell disease. The study provides...

Characterization of Whole Blood Gene Expression Profiles as a Sequel to Globin mRNA Reduction in Patients with Sickle Cell Disease

Raghavachari, Nalini, Xu, Xiuli, Munson, Peter J., Gladwin, Mark T.

Global transcriptome analysis of whole blood RNA using microarrays has been proven to be challenging due to the high abundance of globin transcripts that constitute 70% of whole blood mRNA. This is a...

Nitrite reductase activity of hemoglobin as a systemic nitric oxide generator mechanism to detoxify plasma hemoglobin produced during hemolysis

Minneci, Peter C., Deans, Katherine J., Shiva, Sruti, Zhi, Huang, Banks, Steven M., Kern, Steven, ...

Hemoglobin (Hb) potently inactivates the nitric oxide (NO) radical via a dioxygenation reaction forming nitrate (NO3−). This inactivation produces endothelial dysfunction during hemolytic...

The functional nitrite reductase activity of the heme-globins

Gladwin, Mark T., Kim-Shapiro, Daniel B.

Hemoglobin and myoglobin are among the most extensively studied proteins, and nitrite is one of the most studied small molecules. Recently, multiple physiologic studies have surprisingly revealed...

Nitrite Reductase Activity of Cytochrome c*

Basu, Swati, Azarova, Natalia A., Font, Michael D., King, S. Bruce, Hogg, Neil, Gladwin, Mark T., ...

Small increases in physiological nitrite concentrations have now been shown to mediate a number of biological responses, including hypoxic vasodilation, cytoprotection after ischemia/reperfusion, and...