Biomedical subjects

K Alving

Publications and source records attributed to K Alving.

At least 19 recordsLinked to original sources

PubMed2002

Responses of the bronchial and pulmonary circulations to short-term nitric oxide inhalation before and after endotoxaemia in the pig.

The physiological responses of the bronchial circulation to acute lung injury and endotoxin shock are largely unexplored territory. This study was carried out to study the responsiveness of the bronchial circulation to nitric oxide (NO) inhalation before and after endotoxaemia, in comparison with the pulmonary circulation, as well as to study changes in bronchial blood flow during endotoxaemia. Six anaesthetized pigs (pre-treated with the cortisol-synthesis inhibitor metyrapone) received an infusion of 10 microg/kg endotoxin during 2 h. Absolute bronchial blood flow was measured via an ultrasonic flow probe around the bronchial artery. The pigs received increasing doses of inhaled NO over 5 min each (0, 0.2, 2 and 20 ppm) before and after 4 h of endotoxaemia. The increase in bronchial vascular conductance during 5 min of inhalation of 20 ppm NO before endotoxin shock was significantly higher (area under curve (AUC) 474.2 +/- 84.5% change) than after endotoxin shock (AUC 118.2 +/- 40.4%, P < 0.05 Mann-Whitney U-test). The reduction of the pulmonary arterial pressure by 20 ppm NO was not different. A short rebound effect of the pulmonary arterial pressure occurred after discontinuation of inhaled NO before endotoxaemia (AUC values above baseline 54.4 +/- 19.7% change), and was virtually abolished after endotoxaemia (AUC 6.1 +/- 4.0%, P = 0.052, Mann-Whitney U-test). Our results indicate that the responsiveness of the bronchial circulation to inhalation of increasing doses of inhaled NO during endotoxin shock clearly differ from the responsiveness of the pulmonary circulation. The reduced responsiveness of the bronchial circulation is probably related to decreased driving pressure for the bronchial blood flow. The absence of the short rebound effect on pulmonary arterial pressure (PAP) after induction of shock could be related to maximum constriction of the pulmonary vessels at 4 h.

Administration, Inhalation↗

PubMed2002

The tryptase inhibitor APC-366 reduces the acute airway response to allergen in pigs sensitized to Ascaris suum.

BACKGROUND: Tryptase is a mast cell serine protease that is released during mast cell degranulation. It has been implicated as an important enzyme in the pathophysiology of asthma, but its role in this disease is not fully elucidated. OBJECTIVE: In this study, we investigated the effects of a tryptase inhibitor, APC-366, on the acute allergic airway reaction in specific pathogen-free pigs sensitized to the antigen Ascaris suum. METHODS: APC-366 (5 mg in 1 mL of water, each dose) was given as an aerosol to seven pigs two times (t); at t = - 60 min and t = - 15 min Control pigs received water. Ascaris antigen (in 2 mL saline) was nebulized to the airways over approximately 5 min at t = 0. All aerosols were generated with an ultrasonic nebulizer. RESULTS: The allergen challenge caused an acute reaction with a significant increase in airway resistance (R(aw)) in the control pigs from 3.3 +/- 0.6 cmH20/l/s to 10.2 +/- 2.3 cmH20/l/s, while in the APC-366-treated pigs, the R(aw) increased from 2.6 +/- 0.4 cmH20/l/s to 4.5 +/- 0.7 cmH20/l/s (P < 0.05 compared to controls). The dynamic lung compliance (C(dyn)) decreased significantly in the control pigs, but not in the APC-366-treated animals. The histamine concentration in urine in the control pigs was elevated immediately after allergen challenge, while this release was markedly reduced in the APC-366-treated pigs. CONCLUSION: The tryptase inhibitor APC-366 reduces the acute airway response to allergen significantly. There is also a reduced elevation in urine histamine concentration after challenge in the treated pigs, compared to controls. These results indicate that inhibition of mast cell tryptase might be a useful anti-allergic treatment in asthma.

Airway Resistance↗

PubMed2002

Endothelin-induced vascular and bronchial effects in pig airways: role in acute allergic responses.

The effects of endothelin (ET) agonists on airway mechanics and bronchial blood flow were studied as well as the effects of mixed ET-receptor antagonist bosentan on allergen-induced airway reactions in the pig. ET agonists [ET-1, ET-3, and the ET(B) receptor-selective agonist Sarafotoxin 6c (Sf6c)] were given as intravenous injections (0.4-200 pmol/kg) to eight anesthetized pigs. Bosentan (10 mg/kg iv) was then administered, and the injections were repeated. Only Sf6c caused a significant increase in airway resistance, and this response was blocked by bosentan. Sf6c and ET-1 (200 and 400 pmol/kg, respectively) were also given as aerosols to five pigs. Sf6c, but not ET-1, caused bronchoconstriction via this route. All agonists (intravenous) caused increases in bronchial vascular conductance, an effect that was blocked by an NO-synthase inhibitor (N(G)-nitro-L-arginine) but unaffected by a cyxlooxygenase inhibitor (diclofenac). Fourteen pigs were sensitized with ascaris suum antigen. Under anesthesia, eight pigs were pretreated with bosentan, and six pigs were controls. They were all challenged with allergen aerosol resulting in acute bronchoconstriction and elevation of ET-1 in bronchoalveolar lavage fluid. Bosentan did not affect the maximal acute airway obstruction but markedly increased baseline bronchial vascular conductance, suggesting a basal vascular tone regulated by ETs. In conclusion, ETs induce bronchoconstriction primarily via the ET(B) receptor in the pig. However, ETs are probably not involved in the allergen-induced acute bronchoconstriction in this model.

Acute Disease↗

PubMed2002

Exhaled carbon monoxide is not elevated in patients with asthma or cystic fibrosis.

Increased levels of exhaled carbon monoxide (fractional concentration of CO in expired gas (FE,CO)), measured with an electrochemical sensor, have been reported in patients with inflammatory airway disorders, such as asthma, rhinitis and cystic fibrosis. This study aimed to evaluate these findings by using a fast-response nondisperse infrared (NDIR) analyser, and to compare these measurements with the fractional concentration of nitric oxide in exhaled air (FE,NO). Thirty-two steroid-naïve asthmatics, 24 steroid-treated asthmatics (16 patients with allergic rhinitis, nine patients with cystic fibrosis), and 30 nonsmoking healthy controls were included. CO measurements with the NDIR analyser were performed simultaneously with nitric oxide (NO) analysis (chemiluminescence technique). After 15 s of breath-hold, single-breath exhalations over 10 s were performed at two flow rates and end-tidal plateau concentrations were registered. An electrochemical CO sensor was used independently with an exhalation to residual volume, after a 15 s breath-hold. None of the two CO analysers gave a significant increase in FE,CO in the groups of patients with inflammatory airway disorders compared to controls. FE,NO was significantly elevated in steroid-naïve asthmatics and subjects with allergic rhinitis, but not in steroid-treated asthmatics and subjects with cystic fibrosis. Reducing exhalation flow rate by 50% gave a two-fold increase in FE,NO, while FE,CO was unaffected. A significant increase was seen in FE.CO, but not in FE,NO, when comparing with and without a 10 s breath-hold. In conclusion, the fractional concentration of carbon monoxide in expired gas was not increased in any of the patient groups, while the fractional concentration of nitric oxide in expired gas was significantly elevated in patients with steroid-naïve asthma and allergic rhinitis. Moreover, carbon monoxide was unaffected by flow rate but increased with breath-hold, suggesting an origin in the alveoli rather than the conducting airways.

Adolescent↗

PubMed2002

Nasal and oral contribution to inhaled and exhaled nitric oxide: a study in tracheotomized patients.

Nitric oxide (NO) is produced at different sites in the human airways and may have several physiological effects. Orally-produced NO seems to contribute to the levels found in exhaled air. Autoinhalation of nasal NO increases oxygenation and reduces pulmonary artery pressure in humans. The aim of this study was to measure the concentration and output of NO during nasal, oral and tracheal controlled exhalation and inhalation. Ten tracheotomized patients and seven healthy subjects were studied. The mean+/-SEM fraction of exhaled NO from the nose, mouth and trachea was 56+/-8, 14+/-4 and 6+/-1 parts per billion (ppb), respectively. During single-breath nasal, oral and tracheal inhalation the fraction of inhaled NO was 64+/-14, 11+/-3 and 4+/-1, respectively. There was a marked flow dependency on nasal NO output in the healthy subjects, which was four-fold greater at the higher flow rates, during inhalation when compared to exhalation. There is a substantial contribution of nasal and oral nitric oxide during both inhalation and exhalation. Nasal nitric oxide output is markedly higher during inhalation, reaching levels similar to those that are found to have clinical effects in the trachea. These findings have implications for the measurement of nitric oxide in exhaled air and the physiological effects of autoinhaled endogenous nitric oxide.

Adult↗

PubMed2002

Nitric oxide but not carbon monoxide is continuously released in the human nasal airways.

Results from different laboratories indicate that nitric oxide (NO) and carbon monoxide (CO) coexist in the human airways both in health and disease. These gases are present in exhaled human breath and high concentrations of NO as well as CO have been reported in the nasal airways. In addition, exhaled CO and NO are increased in patients with airways inflammation. NO and CO were measured simultaneously in orally exhaled air and in air sampled from the nose in 18 healthy subjects using chemiluminescence (for NO) and infrared (for CO) techniques at different fixed flow rates. The acute effects of smoking on airway release of NO and CO were also studied. Nasal NO was detected in all subjects and the concentrations were highly flow-dependent (mean+/-SEM: 236+/-23 and 527+/-49 parts per billion (ppb), at 2 and 0.5 L x min(-1), respectively). In contrast, no evidence of CO release in the nasal airways regardless of sample flow rate was found. In fact, additional experiments indicated a net absorption of CO when low levels of this gas were flushed through the nasal cavity. Nasal CO also remained undetectable after smoking. Both NO (22+/-2 ppb) and CO (1.1+/-0.1 parts per million) were consistently found in orally exhaled air. CO, but not NO, levels increased acutely after smoking a cigarette. The authors conclude that the patterns of nitric oxide and carbon monoxide release in the airways seem to differ profoundly in healthy subjects. Orally exhaled air contains both nitric oxide and carbon dioxide whereas nasal air contains nitric oxide only.

Adult↗

PubMed2001

Heparin antagonists are potent inhibitors of mast cell tryptase.

Tryptase may be a key mediator in mast cell-mediated inflammatory reactions. When mast cells are activated, they release large amounts of these tetrameric trypsin-like serine proteases. Tryptase is present in a macromolecular complex with heparin proteoglycan where the interaction with heparin is known to be essential for maintaining enzymatic activity. Recent investigations have shown that tryptase has potent proinflammatory activity, and inhibitors of tryptase have been shown to modulate allergic reactions in vivo. Many of the tryptase inhibitors investigated previously are directed against the active site. In the present study we have investigated an alternative approach for tryptase regulation. We show that the heparin antagonists Polybrene and protamine are potent inhibitors of both human lung tryptase and of recombinant mouse tryptase (mouse mast cell protease 6). Protamine inhibited tryptase in a competitive manner whereas Polybrene showed noncompetitive inhibition kinetics. Treatment of tetrameric, active tryptase with Polybrene caused dissociation into monomers, accompanied by complete loss of enzymatic activity. The present report thus suggests that heparin antagonists potentially may be used in treatment of mast cell-mediated diseases such as asthma.

Animals↗

PubMed2001

Quantitative analysis of bacterial and mammalian proteomes using a combination of cysteine affinity tags and 15N-metabolic labeling.

We describe the combined use of 15N-metabolic labeling and a cysteine-reactive biotin affinity tag to isolate and quantitate cysteine-containing polypeptides (Cys-polypeptides) from Deinococcus radiodurans as well as from mouse B16 melanoma cells. D. radiodurans were cultured in both natural isotopic abundance and 15N-enriched media. Equal numbers of cells from both cultures were combined and the soluble proteins extracted. This mixture of isotopically distinct proteins was derivatized using a commercially available cysteine-reactive reagent that contains a biotin group. Following trypsin digestion, the resulting modified peptides were isolated using immobilized avidin. The mixture was analyzed by capillary reversed-phase liquid chromatography (LC) online with ion trap mass spectrometry (MS) as well as Fourier transform ion cyclotron resonance (FTICR) MS. The resulting spectra contain numerous pairs of Cyspolypeptides whose mass difference corresponds to the number of nitrogen atoms present in each of the peptides. Designation of Cys-polypeptide pairs is also facilitated by the distinctive isotopic distribution of the 15N-labeled peptides versus their 14N-labeled counterparts. Studies with mouse B16 cells maintained in culture allowed the observation of hundreds of isotopically distinct pairs of peptides by LC-FTICR analysis. The ratios of the areas of the pairs of isotopically distinct peptides showed the expected 1:1 labeling of the 14N and 15N versions of each peptide. An additional benefit from the present strategy is that the 15N-labeled peptides do not display significant isotope-dependent chromatographic shifts from their 14N-labeled counterparts, therefore improving the precision for quantitating peptide abundances. The methodology presented offers an alternate, cost-effective strategy for conducting global, quantitative proteomic measurements.

Animals↗

PubMed2001

A new technique for unbiased external ion accumulation in a quadrupole two-dimensional ion trap for electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry.

External ion accumulation in a two-dimensional (2D) multipole trap has been shown to increase the sensitivity, dynamic range and duty cycle of a Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. However, it is important that trapped ions be detected without significant bias at longer accumulation times in the external 2D multipole trap. With increasing ion accumulation time pronounced m/z discrimination was observed when trapping ions in an accumulation quadrupole. In this work we show that superimposing lower rf-amplitude dipolar excitation over the main rf-field in the accumulation quadrupole results in disruption of the m/z discrimination and can potentially be used to achieve unbiased external ion accumulation with FTICR.

Angiotensin I↗

PubMed2001

Optimal pressure conditions for unbiased external ion accumulation in a two-dimensional radio-frequency quadrupole for Fourier transform ion cyclotron resonance mass spectrometry.

When combined with on-line separations (e.g., capillary liquid chromatography (LC)), Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) provides a powerful tool for biological applications, and particularly proteomic studies. The sensitivity, dynamic range, and duty cycle provided by FTICR-MS have been shown to be increased by ion trapping and accumulation in a two-dimensional (2D) radio-frequency (rf)-only multipole positioned externally to an FTICR cell. However, it is important that ions be detected across the desired m/z range without a significant bias. In this work we found that pressure inside the accumulation rf-quadrupole plays an important role in obtaining "unbiased" ion accumulation. Pressure optimization was performed in both pulsed and continuous modes. It was found that unbiased accumulation in a 2D rf-only quadrupole could be achieved in the pressure range of 5 x 10(-4) to 5 x 10(-3) Torr. External ion accumulation performed at the optimal pressure resulted in an increase in both the spectrum acquisition rates and dynamic range.

Algorithms↗

PubMed2001

Nitric oxide inhibition of renal vasoconstrictor responses to sympathetic cotransmitters in the pig in vivo.

The object of the present study was to investigate the involvement of nitric oxide (NO) in the regulation of renal vasoconstrictor responses to sympathetic nerve activation, and each of the known sympathetic cotransmitters separately, in the pig in vivo. Renal vasoconstrictor responses were elicited by sympathetic nerve stimulation, the alpha(1)-adrenoceptor agonist phenylephrine (10 nmol kg(-1), injected iv), neuropeptide Y (NPY, 120 pmol kg(-1), iv) acting on the NPY Y(1) receptor, and the stable ATP-analogue alpha,beta-methylene ATP (mATP, 10 nmol kg(-1)) presumably acting on the P2X(1) purinoceptor. Infusion of the NO-donor sodium nitroprusside, at a dose (0.1 mg kg(-1) h(-1), iv) that elevated renal blood flow (by 14 +/- 7%) and lowered mean arterial pressure (by 30 +/- 5%), inhibited renal vasoconstrictor responses to sympathetic nerve stimulation, phenylephrine, and NPY, but not to mATP. In contrast, injection of the NO synthase inhibitor Nomega-nitro-l-arginine methyl ester, at a dose (10 mg kg(-1), iv) that lowered renal blood flow (by 47 +/- 4%) and elevated mean arterial pressure (by 28 +/- 8%), potentiated the renal vasoconstriction evoked by sympathetic nerve stimulation, phenylephrine, and NPY, but not mATP. It is concluded that endogenous NO may function as an inhibitory modulator of vasoconstrictor responses to the sympathetic cotransmitters norepinephrine and NPY. In contrast, NO seems not to modify vasoconstrictor responses to the sympathetic cotransmitter ATP, a discrepancy that may be due to differences in the types of receptors and intracellular effector mechanisms.

Animals↗

PubMed2001

The effect of a bradykinin B2 receptor antagonist, NPC-567, on allergen-induced airway responses in a porcine model.

OBJECTIVE AND DESIGN: In order to assess the effect of selective blocking of the bradykinin (BK) B2 receptor in allergic airway reactions, the BK B2 receptor antagonist NPC-567 was administered to sensitized pigs before allergen challenge. MATERIAL: Fourteen specific pathogen-free pigs sensitized to Ascaris suum were used. TREATMENT: NPC-567 (2.5 mg, in 1 ml saline) was delivered as an aerosol twice to six pigs. METHODS: Ascaris antigen (in 2 ml saline) was given as an aerosol to all pigs and airway mechanics were monitored for 8 h. NPC-567 (2.5 mg) was given at t = -30 min (in 1ml saline) and mixed with the antigen at t = 0 to six pigs. RESULTS: Allergen challenge caused an acute reaction with a rapid, significant increase in airways resistance from 4.1 +/- 0.5 cm H2O/l/s to a maximum of 16.2 +/- 3.0 cm H2O/l/s in the control pigs. In the NPC-567-treated pigs, the resistance only increased from 2.9 +/- 0.3 cm H2O/l/s to 6.5 +/- 0.9 cm H2O/l/s (p<0.005 compared to controls). There was also a higher reduction in dynamic lung compliance in the controls than in the treated animals upon allergen challenge. The histamine concentration in urine in the control pigs was markedly elevated after allergen challenge peaking at 15-30 min. This release was inhibited in the NPC-567-treated pigs. CONCLUSIONS: The BK B2 receptor antagonist NPC-567 seems to be effective in inhibiting the acute response to allergen in the pig airways, possibly due to inhibition of mast cell activation via indirect mechanisms. The late obstructive response was reduced as well, probably as a consequence of the reduced mediator release in the acute reaction.

Aerosols↗

PubMed2001

Limitation of infarct size and attenuation of myeloperoxidase activity by an endothelin A receptor antagonist following ischaemia and reperfusion.

It has previously been shown that endothelin (ET) receptor antagonists limit myocardial ischaemia/reperfusion (I/R) injury. The mechanism behind this effect is still unclear. The aim of this study was to elucidate the possible relationship between cardioprotection by an ET(A) receptor antagonist and inhibition of neutrophil accumulation or activation in the myocardium determined as myeloperoxidase (MPO) activity during I/R. Anaesthetised pigs were subjected to 45 min ischaemia by ligation of the left anterior descending coronary artery (LAD) followed by 4 h of reperfusion. Infiltration of MPO-containing cells, presumably neutrophils, into the ischaemic area was confirmed with an immunohistochemical technique using antibodies against porcine MPO. Vehicle (n = 7) or the selective ET(A) receptor antagonist LU 135252 (LU; n = 7) were given into the LAD during the last 10 min of ischaemia and the first 5 min of reperfusion. There were no significant differences in LAD flow, mean arterial pressure, heart rate, or rate pressure product between the groups during I/R. The area at risk was similar in the two groups. LU reduced the final infarct size to 40+/-6% of the area at risk compared to 80+/-6% in the vehicle group (P < 0.001). Endothelin-like immunoreactivity increased 2-fold in the ischaemic area in the vehicle group (P < 0.01), but not in the group given LU. MPO activity was higher (2.5x) in the ischaemic than in the non-ischaemic myocardium of the vehicle group. The MPO activity in the ischaemic myocardium was significantly lower in the group given LU (7.0+/-1.2 units g(-1)) than in the vehicle group (14.2+/-1.9 units g(-1); P < 0.01). There was a significant correlation between the infarct size and MPO activity (P < 0.01, r = 0.68). In conclusion, local administration of the selective ET(A) receptor antagonist LU during the last period of ischaemia and early reperfusion reduces the extent of myocardial necrosis and MPO activity. This suggests that LU may exert its cardioprotective effect by inhibiting neutrophil-mediated injury.

Animals↗

PubMed2001

Effects of the endothelin receptor antagonist bosentan on cardiac performance during porcine endotoxin shock.

BACKGROUND: Cardiac dysfunction during septic shock is well described but the underlying mechanisms still remain to be resolved. This study was conducted to elucidate the involvement of endothelin in cardiac function during endotoxin shock by the use of endothelin receptor antagonism. METHODS: Anaesthetised and haemodynamically stable landrace pigs received the nonpeptide mixed endothelin receptor antagonist bosentan, two hours after onset of endotoxaemia (n=7). Cardiopulmonary vascular changes, including cardiac index, stroke work index, coronary artery blood flow, rate of change of left ventricular pressure (dp/dt), and arterial and coronary sinus plasma levels of endothelin-1-like immunoreactivity were compared to a control group only receiving endotoxin (n=7). RESULTS: Plasma endothelin-1-like immunoreactivity increased threefold in the control group. Bosentan effectively counteracted the endotoxin induced decrease in cardiac index. This was accompanied by a significant reduction of both right and left ventricular afterload. In addition, coronary artery blood flow increased and coronary vascular resistance decreased compared to controls. Dp/dt remained unaffected by endothelin receptor antagonism. A further increase in plasma endothelin-1-like immunoreactivity was seen in response to bosentan. CONCLUSION: These results indicate that the increased endothelin production during endotoxaemia contributes to a depressed cardiac performance and that endothelin receptor antagonism may counteract this development. Possible mechanisms for the improved cardiac performance include both a reduction of afterload and enhanced coronary blood flow.

Animals↗

PubMed2001

Nitrite-derived nitric oxide: a possible mediator of 'acidic-metabolic' vasodilation.

The fundamental, yet poorly understood, physiological mechanism known as 'acidic-metabolic' vasodilation, contributes to local blood flow regulation during hypoxia/ischaemia and increased metabolic activity. The vasodilator nitric oxide (NO) has been suggested to be involved in this event. Besides enzymatic production by NO synthases, a novel mechanism for generation of this gas in vivo was recently described. This involves non-enzymatic reduction of inorganic nitrite to NO, a reaction that takes place predominantly during acidic/reducing conditions. We have studied the effects of physiological amounts of nitrite on NO generation and relaxation of rat aorta in vitro in a situation where environmental pH was reduced to levels seen in tissues during hypoxia/ischaemia. The relaxatory effect of nitrite was increased in an acidic buffer solution (pH 6.6) compared with neutral pH; EC50 for nitrite was reduced from 200 to 40 microM. Nitrite-evoked relaxation was effectively prevented by coadministration of an inhibitor of soluble guanylyl cyclase. The relaxation was further potentiated by the addition of ascorbic acid. In parallel, NO was generated from nitrite in a pH dependent manner with even larger amounts seen after addition of ascorbic acid. NO generation from nitrite correlated to the the degree of relaxation of rat aorta. These results illustrate non-enzymatic release of NO from nitrite at physiological concentrations. This may be an important auto-regulated physiological mechanism involved in the regulation of vascular tone during hypoxia/ischaemia.

Acidosis↗

PubMed2001

Selective protective effects of nitric oxide inhalation on allergen-induced acute airway reactions in the pig.

BACKGROUND: Nitric oxide (NO) is thought to be an important mediator of inflammatory processes during allergic reactions in the respiratory tract. OBJECTIVE: This study was undertaken to investigate the effects of inhalation of NO on the allergen-induced acute airway reactions in the pig. METHODS: Specific pathogen-free pigs were sensitized with Ascaris suum antigen and challenged with an allergen aerosol during mechanical ventilation and anaesthesia. One group (n = 8) was treated with inhaled NO (20 ppm) which was given from 30 min before allergen challenge until the experiments were completed at 120 min after challenge. A control group (n = 8) did not receive NO (< 0.001 ppm). RESULTS: Inhalation of 20 ppm NO prevented the fall in arterial pO2/FiO2 levels that was observed in the control group (areas under the curve between 0 and 120 min were 3.7 +/- 1.4 kPa/min in NO-treated pigs vs. 15.9 +/- 3.4 in controls, P < 0.01, Mann-Whitney U-test) and it decreased baseline pulmonary arterial pressure (change from time-point - 30-0 was 3.1 +/- 5.3% in the control and - 19.9 +/- 3.5% in the NO group, P < 0.01), which in turn resulted in a lower pulmonary arterial pressure during allergen challenge. NO also caused vasodilatation in the bronchial circulation, resulting in increased bronchial vascular conductance throughout the experiment. NO inhalation caused a small, but non-significant, reduction in the allergen-induced bronchoconstrictor response, whereas histamine release, as detected in urine, was not changed. Total protein levels in bronchoalveolar lavage (BAL) fluid were significantly decreased in the NO group at 120 min after challenge compared with 45 min (373 +/- 101 microg/mL vs. 631 +/- 184, respectively, P < 0.05, Wilcoxon matched pairs test), whereas levels in the control group did not change between these two time-points (513 +/- 282 vs. 599 +/- 354, not significant). CONCLUSION: These findings indicate that NO inhalation improves ventilation/perfusion matching and causes some bronchodilatation during the allergen-induced acute airway reaction, whereas histamine release is not affected. Moreover, NO inhalation enhanced the clearance of extravasated protein in the airways, possibly through increased bronchial blood flow. Even though some protective effects were seen, this study does not support a therapeutic role for exogenous NO in acute allergic reactions.

Administration, Inhalation↗

PubMed2001

Increased nitric oxide in exhaled air after intake of a nitrate-rich meal.

Exhaled and nasal NO (ENO, NNO) have been suggested as markers for inflammation in lower and upper respiratory tract respectively. It is still unknown how a number of factors, apart from airway inflammation, can influence NO levels. The aim of this study was to determine the effect of a nitrate-rich meal on ENO and NNO. Sixteen healthy subjects were observed during 1 week on normal diet before a nitrate-restricted diet was introduced in the next. On day 3 of the second week they were made to ingest a nitrate rich meal. ENO, NNO, plasma nitrate and plasma L-arginine were followed before the meal and afterwards for 3 h. ENO and NNO as well as plasma nitrate and plasma L-arginine were significantly elevated after the nitrate-rich meal. The median maximal increase of ENO and NNO was 47% and 13% respectively. We found a moderate but significant correlation between the rise in plasma nitrate and ENO (r(s)=0.57, P=0.027) but none between plasma nitrate and NNO (r(s)=-0.02, P=0.95). As nitrate in the diet seems to substantially influence the levels of ENO it is important either to restrict or register the intake of nitrate-rich food prior to measuring ENO.

Adult↗

PubMed2001

Endothelin-1 and nitric oxide synthase in short rebound reaction to short exposure to inhaled nitric oxide.

On withdrawal of inhalation of nitric oxide (INO) administered after lung injury, pulmonary artery pressure (PAP) and arterial oxygen tension (Pa(O(2))) may deteriorate more than before INO (rebound response). In this study, we investigated the possible roles of endothelin (ET)-1 and nitric oxide (NO) synthase (NOS) activity in the short rebound reaction to short-term inhalation of NO. Twenty-six anesthetized mechanically ventilated piglets were given endotoxin infusion. Twelve animals then received INO (30 parts per million) for two 30-min periods. Nine controls were not given NO. Measurements were made of blood gases and hemodynamic parameters, lung tissue ET-1 expression and NOS activity, and plasma ET-1 concentration. INO decreased PAP and increased Pa(O(2)), but INO withdrawal caused a short rebound reaction with an increase in PAP. Lung tissue expression and plasma concentration of ET-1 increased during INO, and plasma ET-1 increased further after its withdrawal. Activity of constitutive NOS decreased during INO, whereas that of inducible NOS was unchanged. Upregulation of ET-1 and downregulation of NOS activity may have influenced the short rebound reaction to short-term INO.

Administration, Inhalation↗