bluuebunny/crossref_metadata_2025_split huggingface dataset:
Angiotensin II reduces infarct size and has no effect on post‐ischaemic contractile dysfunction in isolated rat hearts
Authors: Ford William R , Clanachan Alexander S , Robin Hiley C , Jugdutt Bodh I 
Published: January 2005

In order to test the hypothesis that angiotensin II exacerbates myocardial ischaemia‐reperfusion (IR) injury, we examined the effects of graded angiotension II concentrations of angiotensin II on IR injury in both working and non‐working (Langendorff) isolated rat hearts.
Non‐working hearts were subjected to 30 min aerobic perfusion (baseline) then 25 min of global, no‐flow ischaemia followed by 30 min of reperfusion either in the absence (control, n=7) or presence of 1 (n=6) or 10 nM (n=5) angiotensin II). Recoveries of LV developed pressure and coronary flow after 30 min reperfusion in control hearts (58±9 and 40±8% of baseline levels, respectively) were no different from hearts treated with 1 or 10 nM angiotensin II. Infarct size (determined at the end of reperfusion by triphenyltetrazolium chloride staining) was reduced by angiotensin II in a concentration‐dependent manner (from a control value of 27±3 to 18±4% and 9±3% of the LV, respectively).
Working hearts were subjected to 50 min pre‐ischaemic (pre‐I) aerobic perfusion then 30 min of global, no‐flow ischaemia followed by 30 min of reperfusion either in the absence (control, n=14) or presence of 1 (n=8), 10 (n=7) or 100 nM (n=7) angiotensin II). In controls, post‐ischaemic (post‐I) left ventricular (LV) work and efficiency of oxygen consumption were depressed (43±9 and 42±10% of pre‐I levels, respectively). The presence of angiotensin II throughout IR had no effect on LV work compared with control.
Thus, angiotensin II reduces infarct size in a concentration‐dependent manner but has no effect on contractile stunning associated with IR in isolated rat hearts.

British Journal of Pharmacology (2001) 134, 38–45; doi:10.1038/sj.bjp.0704225
Suppression of granulocyte/macrophage colony‐stimulating factor release from human monocytes by cyclic AMP‐elevating drugs: role of interleukin‐10
Authors: Seldon Paul M , Giembycz Mark A 
Published: January 2005

Granulocyte/macrophage colony‐stimulating factor (GM‐CSF) is a pro‐inflammatory cytokine secreted by cells of the monocyte/macrophage lineage and has been implicated in the pathogenesis of bronchitis and asthma.
In the present study we have evaluated the effect of several cyclic AMP‐elevating agents on lipopolysaccharide (LPS)‐induced GM‐CSF release from human monocytes and the extent to which the anti‐inflammatory cytokine, interleukin (IL)‐10, is involved.
LPS evoked a concentration‐dependent generation of GM‐CSF from human monocytes that was inhibited, at the mRNA and protein level, by 8‐Br‐cyclic AMP, cholera toxin, prostaglandin E2 (PGE2) and a number of structurally dissimilar phosphodiesterase (PDE) 4 inhibitors.
Pre‐treatment of monocytes with a concentration of an anti‐IL‐10 monoclonal antibody that abolished the inhibitory action of a maximally effective concentration of exogenous human recombinant IL‐10, significantly augmented LPS‐induced GM‐CSF generation. This effect was associated with a parallel upwards displacement of the concentration‐response curves that described the inhibition of GM‐CSF by PGE2, 8‐Br‐cyclic AMP and the PDE4 inhibitor, rolipram, without significantly changing the potency of any drug. Consequently, the maximum percentage inhibition of GM‐CSF release was reduced. Further experiments established that the reduction in the maximum inhibition of GM‐CSF release seen in anti‐IL‐10‐treated cells was not due to functional antagonism as rolipram, PGE2 and 8‐Br‐cyclic AMP were equi‐effective at all concentrations of LPS studied.
These data indicate that cyclic AMP‐elevating drugs attenuate the elaboration of GM‐CSF from LPS‐stimulated human monocytes by a mechanism that is not mediated via IL‐10. Suppression of GM‐CSF from monocytes may explain, at least in part, the efficacy of PDE4 inhibitors in clinical trials of chronic obstructive pulmonary disease.

British Journal of Pharmacology (2001) 134, 58–67; doi:10.1038/sj.bjp.0704238
Analysis of GABAA‐ and GABAB‐receptor mediated effects on intracellular Ca2+ in DRG hybrid neurones
Authors: Yokogawa Tomonori , Kim Seung U , Krieger Charles , Puil Ernest 
Published: January 2005

Using pharmacological analysis and fura‐2 spectrofluorimetry, we examined the effects of γ‐aminobutyric acid (GABA) and related substances on intracellular Ca2+ concentration ([Ca2+]i) of hybrid neurones, called MD3 cells. The cell line was produced by fusion between a mouse neuroblastoma cell and a mouse dorsal root ganglion (DRG) neurone.
MD3 cells exhibited DRG neurone‐like properties, such as immunoreactivity to microtubule‐associated protein‐2 and neurofilament proteins. Bath applications of capsaicin and α, β‐methylene adenosine triphosphate reversibly increased [Ca2+]i. However, repeated applications of capsaicin were much less effective.
Pressure applications of GABA (100 μM), (Z)‐3‐[(aminoiminomethyl) thio] prop‐2‐enoic acid sulphate (ZAPA; 100 μM), an agonist at low affinity GABAA‐receptors, or KCl (25 mM), transiently increased [Ca2+]i.
Bath application of bicuculline (100 nM – 100 μM), but not picrotoxinin (10 – 25 μM), antagonized GABA‐induced increases in [Ca2+]i in a concentration‐dependent manner (IC50=9.3 μM).
Ca2+‐free perfusion reversibly abolished GABA‐evoked increases in [Ca2+]i. Nifedipine and nimodipine eliminated GABA‐evoked increases in [Ca2+]i. These results imply GABA response dependence on extracellular Ca2+.
Baclofen (500 nM – 100 μM) activation of GABAB‐receptors reversibly attenuated KCl‐induced increases in [Ca2+]i in a concentration‐dependent manner (EC50=1.8 μM). 2‐hydroxy‐saclofen (1 – 20 μM) antagonized the baclofen‐depression of the KCl‐induced increase in [Ca2+]i.
In conclusion, GABAA‐receptor activation had effects similar to depolarization by high external K+, initiating Ca2+ influx through high voltage‐activated channels, thereby transiently elevating [Ca2+]i. GABAB‐receptor activation reduced Ca2+ influx evoked by depolarization, possibly at Ca2+‐channel sites in MD3 cells.

British Journal of Pharmacology (2001) 134, 98–107; doi:10.1038/sj.bjp.0704244
Inhibitory effects of brefeldin A, a membrane transport blocker, on the bradykinin‐induced hyperpolarization‐mediated relaxation in the porcine coronary artery
Authors: Ohnishi Yoshinori , Hirano Katsuya , Nishimura Junji , Furue Masutaka , Kanaide Hideo 
Published: January 2005

To elucidate the mechanism of the relaxation mediated by endothelium‐derived hyperpolarizing factors (EDHFs), the effect of brefeldin A, a membrane transport blocker, on cytosolic Ca2+ concentration ([Ca2+]i) and tension was determined in the porcine coronary arterial strips. We also examined the effect of brefeldin A on [Ca2+]i in the endothelial cells of the porcine aortic valve.
In the presence of 10 μM indomethacin and 30 μM NG‐nitro‐L‐arginine (L‐NOARG), both bradykinin and substance P induced a transient decrease in [Ca2+]i and tension in arterial strips contracted with 100 nM U46619 (thromboxane A2 analogue). A 6 h pre‐treatment with 20 μg ml−1 brefeldin A abolished the bradykinin‐induced relaxation, while it had no effect on the substance P‐induced relaxation.
In the absence of indomethacin and L‐NOARG, brefeldin A had no effect on the bradykinin‐induced relaxation during the contraction induced by U46619 or 118 mM K+.
The indomethacin/L‐NOARG‐resistant relaxation induced by bradykinin was completely inhibited by 3 mM tetrabutylammonium (non‐specific Ca2+‐activated K+ channel blocker), while that induced by substance P was not inhibited by 3 mM tetrabutylammonium or 1 mM 4‐aminopyridine (voltage‐dependent K+ channels blocker) alone, but completely inhibited by their combination.
Brefeldin A had no effect on the [Ca2+]i elevation in endothelial cells induced by bradykinin or substance P.
In conclusion, bradykinin produce EDHF in a brefeldin A‐sensitive mechanism in the porcine coronary artery. However, this mechanism is not active in a substance P‐induced production of EDHF, which thus suggests EDHF to be more than a single entity.

British Journal of Pharmacology (2001) 134, 168–178; doi:10.1038/sj.bjp.0704246
Pharmacological and biochemical characterization of A3 adenosine receptors in Jurkat T cells
Authors: Gessi Stefania , Varani Katia , Merighi Stefania , Morelli Anna , Ferrari Davide , Leung Edward , Baraldi Pier Giovanni , Spalluto Giampiero , Borea Pier Andrea 
Published: January 2005

The present work was devoted to the study of A3 adenosine receptors in Jurkat cells, a human leukemia line.
The A3 subtype was found by means of RT‐PCR experiments and characterized by using the new A3 adenosine receptor antagonist [3H]‐MRE 3008F20, the only A3 selective radioligand currently available. Saturation experiments revealed a single high affinity binding site with KD of 1.9±0.2 nM and Bmax of 1.3±0.1 pmol mg−1 of protein.
The pharmacological profile of [3H]‐MRE 3008F20 binding on Jurkat cells was established using typical adenosine ligands which displayed a rank order of potency typical of the A3 subtype.
Thermodynamic data indicated that [3H]‐MRE 3008F20 binding to A3 subtype in Jurkat cells was entropy‐ and enthalpy‐driven, according with that found in cells expressing the recombinant human A3 subtype.
In functional assays the high affinity A3 agonists Cl‐IB‐MECA and IB‐MECA were able to inhibit cyclic AMP accumulation and stimulate Ca2+ release from intracellular Ca2+ pools followed by Ca2+ influx.
The presence of the other adenosine subtypes was investigated in Jurkat cells. A1 receptors were characterized using [3H]‐DPCPX binding with a KD of 0.9±0.1 nM and Bmax of 42±3 fmol mg−1 of protein. A2A receptors were studied with [3H]‐SCH 58261 binding and revealed a KD of 2.5±0.3 nM and a Bmax of 1.4±0.2 pmol mg−1 of protein.
In conclusion, by means of the first antagonist radioligand [3H]‐MRE 3008F20 we could demonstrate the existence of functional A3 receptors on Jurkat cells.

British Journal of Pharmacology (2001) 134, 116–126; doi:10.1038/sj.bjp.0704254
Suppression of K+‐induced hyperpolarization by phenylephrine in rat mesenteric artery: relevance to studies of endothelium‐derived hyperpolarizing factor
Authors: Richards G R , Weston A H , Burnham M P , Félétou M , Vanhoutte P M , Edwards G 
Published: January 2005

In intact mesenteric arteries, increasing [K+]o by 5 mM hyperpolarized both endothelial and smooth muscle cells. Subsequent exposure to 10 μM phenylephrine depolarized both cell types which were then repolarized by a 5 mM increase in [K+]o. In endothelium‐denuded vessels, increasing [K+]o by 5 mM hyperpolarized the smooth muscle but K+ had no effect after depolarization by 10 μM phenylephrine. On subsequent exposure to iberiotoxin plus 4‐aminopyridine, the repolarizing action of 5 mM K+ was restored. In endothelium‐intact vessels exposed to phenylephrine, pretreatment with a gap junction inhibitor (gap 27) reduced K+‐mediated smooth muscle repolarization without affecting the endothelial cell response. It is concluded that phenylephrine‐induced efflux of K+ via smooth muscle K+ channels produces a local increase in [K+]o which impairs repolarization to added K+. Thus, studies involving vessels precontracted with agonists which increase [K+]o maximize the role of gap junctions and minimize any contribution to the EDHF pathway from endothelium‐derived K+.British Journal of Pharmacology (2001) 134, 1–5; doi:10.1038/sj.bjp.0704256
Effects of S‐2474, a novel nonsteroidal anti‐inflammatory drug, on amyloid β protein‐induced neuronal cell death
Authors: Yagami Tatsurou , Ueda Keiichi , Asakura Kenji , Sakaeda Toshiyuki , Kuroda Takayuki , Hata Satoshi , Kambayashi Yoshikazu , Fujimoto Masafumi 
Published: January 2005

The accumulation of amyloid β protein (Aβ) in the brain is a characteristic feature of Alzheimer's disease (AD). Clinical trials of AD patients with nonsteroidal anti‐inflammatory drugs (NSAIDs) indicate a clinical benefit. NSAIDs are presumed to act by suppressing inhibiting chronic inflammation in the brain of AD patients.
In the present study, we investigated effects of S‐2474 on Aβ‐induced cell death in primary cultures of rat cortical neurons. S‐2474 is a novel NSAID, which inhibits cyclo‐oxygenase‐2 (COX‐2) and contains the di‐tert‐butylphenol antioxidant moiety.
S‐2474 significantly prevented neurons from Aβ(25 – 35)‐ and Aβ(1 – 40)‐induced cell death. S‐2474 ameliorated Aβ‐induced apoptotic features such as the condensation of chromatin and the fragmentation of DNA completely.
Prior to cell death, Aβ(25 – 35) generated prostaglandin D2 (PGD2) and free radicals from neurons. PGD2 is a product of cyclo‐oxygenase (COX), and caused neuronal cell death.
S‐2474 significantly inhibited the Aβ(25 – 35)‐induced generation of PGD2 and free radicals.
The present cortical cultures contained little non‐neuronal cells, indicating that S‐2474 affected neuronal survival directly, but not indirectly via non‐neuronal cells. Both an inhibitory effect of COX‐2 and an antioxidant effect might contribute to the neuroprotective effects of S‐2474.
In conclusion, S‐2474 exhibits protective effects against neurotoxicity of Aβ. Furthermore, the present study suggests that S‐2474 may possess therapeutic potential for AD via ameliorating degeneration in neurons as well as suppressing chronic inflammation in non‐neuronal cells.

British Journal of Pharmacology (2001) 134, 673–681; doi:10.1038/sj.bjp.0704261
Vascular smooth muscle relaxation mediated by nitric oxide donors: a comparison with acetylcholine, nitric oxide andnitroxyl ion
Authors: Wanstall Janet C , Jeffery Trina K , Gambino Agatha , Lovren Fina , Triggle Christopher R 
Published: January 2005

Vasorelaxant properties of three nitric oxide (NO) donor drugs (glyceryl trinitrate, sodium nitroprusside and spermine NONOate) in mouse aorta (phenylephrine pre‐contracted) were compared with those of endothelium‐derived NO (generated with acetylcholine), NO free radical (NO·; NO gas solution) and nitroxyl ion (NO−; from Angeli's salt).
The soluble guanylate cyclase inhibitor, ODQ (1H‐(1,2,4‐)oxadiazolo(4,3‐a)‐quinoxalin‐1‐one; 0.3, 1 and 10 μM), concentration‐dependently inhibited responses to all agents. 10 μM ODQ abolished responses to acetylcholine and glyceryl trinitrate, almost abolished responses to sodium nitroprusside but produced parallel shifts (to a higher concentration range; no depression in maxima) in the concentration‐response curves for NO gas solution, Angeli's salt and spermine NONOate.
The NO· scavengers, carboxy‐PTIO, (2‐(4‐carboxyphenyl)‐4,4,5,5‐tetramethyl‐imidazoline‐1‐oxyl‐3‐oxide; 100 μM) and hydroxocobalamin (100 μM), both inhibited responses to NO gas solution and to the three NO donor drugs, but not Angeli's salt. Hydroxocobalamin, but not carboxy‐PTIO, also inhibited responses to acetylcholine.
The NO− inhibitor, L‐cysteine (3 mM), inhibited responses to Angeli's salt, acetylcholine and the three NO donor drugs, but not NO gas solution.
The data suggest that, in mouse aorta, responses to all three NO donors involve (i) activation of soluble guanylate cyclase, but to differing degrees and (ii) generation of both NO· and NO−. Glyceryl trinitrate and sodium nitroprusside, which generate NO following tissue bioactivation, have profiles resembling the profile of endothelium‐derived NO more than that of exogenous NO. Spermine NONOate, which generates NO spontaneously outside the tissue, was the drug that most closely resembled (but was not identical to) exogenous NO.

British Journal of Pharmacology (2001) 134, 463–472; doi:10.1038/sj.bjp.0704269
Guanosine 3′: 5′‐cyclic monophosphate‐dependent pathway alterations in ventricular cardiomyocytes of spontaneously hypertensive rats
Authors: Mazzetti Luca , Ruocco Carlo , Giovannelli Lisa , Ciuffi Mario , Franchi‐Micheli Sergio , Marra Fabio , Zilletti Lucilla , Failli Paola 
Published: January 2005

We investigated the effect of the NO‐donor S‐nitroso‐N‐acetyl‐DL‐penicillamine (SNAP) on cardiomyocytes isolated from control normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats.
Ventricular cardiomyocytes were isolated from SHR and WKY hearts and imaging analysis of fura‐2‐loaded cells was performed in order to evaluate calcium transient in electrical field paced (0.5 Hz) cells.
In WKY cardiomyocytes, 1 – 200 μM SNAP dose‐dependently increased cyclic GMP content. In basal conditions, cyclic GMP content of SHR cardiomyocytes was significantly higher than in WKY, but SNAP failed to further increase cyclic GMP over the basal level.
In control conditions, the ΔF/F and decay time of the calcium transient were similar in both strains. In WKY cardiomyocytes, SNAP (1 – 100 μM) reduced the decay time. In SHR cardiomyocytes, SNAP was ineffective. Dibutyryl cyclic GMP (10−6 – 10−8 M), a membrane permeable cyclic GMP analogue, behaved similarly to SNAP.
In WKY and SHR cardiomyocytes, 10−8 M isoprenaline similarly increased ΔF/F and decreased the decay time. SNAP and dibutyryl cyclic GMP prevented the effect of isoprenaline in WKY, whereas both molecules were ineffective in SHR cardiomyocytes. In WKY, SNAP effects were blocked by pretreating cells with the cGK inhibitor KT‐5823.
Western blotting analysis of cGK type I showed that the enzyme was expressed in WKY isolated cardiomyocytes, but absent in four out of five SHR preparations.
We concluded that the low expression of cGKI may determine the lack of NO/cyclic GMP‐dependent regulation on calcium transient in SHR cardiomyocytes. This alteration may contribute to the development of heart hypertrophy in hypertensive status.

British Journal of Pharmacology (2001) 134, 596–602; doi:10.1038/sj.bjp.0704275
Protective effects of 5‐HT1A receptor agonists against emotional changes produced by stress stimuli are related to their neuroendocrine effects
Authors: Tsuji Minoru , Takeda Hiroshi , Matsumiya Teruhiko 
Published: January 2005

The effects of the 11β‐hydroxylase inhibitor metyrapone on the protective effects of serotonin (5‐hydroxytryptamine; 5‐HT)1A receptor agonists against emotional changes produced by acute restraint stress were examined in mice.
Changes in the emotional state of mice were evaluated in terms of changes in exploratory activity, i.e. total locomotor activity, number and duration of rearing and head‐dipping behaviours, and latency to the first head‐dipping, using an automatic hole‐board apparatus.
Treatment with the 5‐HT1A receptor agonists flesinoxan (1 mg kg−1, i.p.) and R(+)‐2‐di‐n‐propylamino‐8‐hydroxy‐1,2,3,4‐tetrahydronaphthalene hydrobromide (8‐OH‐DPAT; 1 mg kg−1, i.p.) 24 h prior to exposure to stress significantly suppressed the decrease in various exploratory behaviours that was observed immediately after the exposure to acute restraint stress (60 min). The effects of flesinoxan (1 mg kg−1, i.p.) and 8‐OH‐DPAT (1 mg kg−1, i.p.) were antagonized by co‐injection with N‐{2‐[4‐(2‐methoxyphenyl)‐1‐piperazinyl]ethyl}‐N‐(2‐pyridinyl) cyclohexanecarboxamide trihydrochloride (WAY100635; 1 mg kg−1, i.p.), a selective 5‐HT1A receptor antagonist.
Flesinoxan (1 mg kg−1, i.p.) and 8‐OH‐DPAT (1 mg kg−1 i.p.) significantly increased the plasma corticosterone level, and these effects of 5‐HT1A receptor agonists were dose‐dependently blocked by pretreatment with metyrapone (12.5 and 25 mg kg−1, s.c.).
Metyrapone (25 mg kg−1, s.c.) alone did not modify the stress‐induced changes in exploratory behaviours. Pretreatment with metyrapone (12.5 and 25 mg kg−1, s.c.) partly antagonized the protective effects of flesinoxan (1 mg kg−1, i.p.) and 8‐OH‐DPAT (1 mg kg−1, i.p.) with regard to only the number and duration of head‐dipping behaviours.
These results suggest that activation of the adrenocortical system via 5‐HT1A receptors may facilitate some adaptive mechanism(s) involved in the recognition of and/or ability to cope with stressful situations.

British Journal of Pharmacology (2001) 134, 585–595; doi:10.1038/sj.bjp.0704276
Orphanin FQ/nociceptin attenuates the development of morphine tolerance in rats
Authors: Lutfy Kabirullah , Hossain Syed M , Khaliq Imran , Maidment Nigel T 
Published: January 2005

Recent evidence from studies in mice lacking the opioid receptor‐like (ORL‐1) receptor and from experiments using antibodies raised against orphanin FQ/nociceptin (OFQ/N) suggest that this peptide may be involved in morphine tolerance. In the present study we sought to investigate if administration of exogenous OFQ/N would modulate the development of tolerance to the antinociceptive effect of morphine.
Rats were treated for 3 days with either saline or morphine (10 mg kg−1, s.c.) followed, 15 and 75 min later, by two intracerebroventricular injections of either artificial cerebrospinal fluid (aCSF) or OFQ/N. The dose of OFQ/N was doubled each day (7.5, 15, 30 nmol). On day 4, rats were tested on a hot plate apparatus before and 30, 60 and 90 min after morphine administration.
Repeated OFQ/N treatment did not affect basal nociceptive responses or morphine‐induced antinociception. However, the same treatment significantly attenuated the development of morphine tolerance.
Since learning and memory could contribute to the development of morphine tolerance, in subsequent studies, we examined the effect of OFQ/N administered in the CA3 region of the hippocampus, where OFQ/N has been shown to block LTP and impair spatial memory. A greater attenuation of morphine tolerance with no alteration of baseline hot plate latency or morphine‐induced antinociception was observed when OFQ/N was administered in this area of the rat brain.
Taken together, our results demonstrate that OFQ/N may act in the hippocampus to attenuate morphine tolerance.

British Journal of Pharmacology (2001) 134, 529–534; doi:10.1038/sj.bjp.0704279
Effects of agents that inactivate free radical NO (NO•) on nitroxyl anion‐mediated relaxations, and on the detection of NO• released from the nitroxyl anion donor Angeli's salt
Authors: Ellis Anthie , Lu Hong , Li Chun Guang , Rand Michael J 
Published: January 2005

The effects of agents that inactivate free radical nitric oxide (carboxy‐PTIO, hydroxocobalamin and pyrogallol) were tested on relaxations produced by the nitroxyl anion (NO−) donor Angeli's salt in rat aortic rings and anococcygeus muscles. The amount of NO• generated from Angeli's salt in the presence of these agents was measured using a NO•‐selective electrode sensor.
Carboxy‐PTIO (100, 300 μM), hydroxocobalamin (30, 100 μM) and pyrogallol (10, 30 μM) significantly reduced relaxations produced by Angeli's salt (0.3 μM) in aortic rings but not in anococcygeus muscles.
NO• generated from Angeli's salt (0.1 – 10 μM), as detected by the sensor electrode, was less than 0.5% of the amount of Angeli's salt added. Carboxy‐PTIO (100 μM) and hydroxocobalamin (30 μM), but not pyrogallol significantly increased the amount of NO• detected.
In the presence of an oxidizing agent copper [II] (as CuSO4 100 μM), the amount of NO• detected from 0.3 μM of Angeli's salt increased from an undetectable level of 142.7±15.7 nM (equivalent to 47.6% of Angeli's salt added). Under these conditions, carboxy‐PTIO, hydroxocobalamin and pyrogallol significantly reduced the amount of NO• detected from Angeli's salt as well as the signal generated by an equivalent amount of authentic NO (0.33 μM).
The difference in effects of these agents on relaxations to Angeli's salt in the aorta and the anococcygeus muscle may be explained by the ready conversion of NO− to NO• in the aorta through an unidentified mechanism, which makes NO− susceptible to inactivation by these agents. Furthermore, in addition to inactivating NO•, carboxy‐PTIO and hydroxocobalamin may themselves oxidize NO− to NO•, albeit slightly.

British Journal of Pharmacology (2001) 134, 521–528; doi:10.1038/sj.bjp.0704287