PubMed Health⌕ Search

Biomedical subjects

L E Gustafsson

Publications and source records attributed to L E Gustafsson.

At least 37 records · Page 2Linked to original sources
PubMed1998

Blockade of nitrergic neuroeffector transmission in guinea-pig colon by a selective inhibitor of soluble guanylyl cyclase.

The role of soluble guanylyl cyclase in nitrergic inhibitory neuroeffector transmission was investigated in the longitudinal muscle from guinea-pig colon, by using an inhibitor of soluble guanylyl cyclase, 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ). In preparations precontracted with histamine, electrical field stimulation (EFS) or exogenous nitric oxide (NO) induced relaxations. The relaxation induced by NO-application was abolished by ODQ. Both ODQ and the NO-synthase inhibitor N omega-nitro-L-arginine (L-NOARG) partially inhibited the EFS-evoked relaxation to a similar extent. These effects were dose-dependent. The inhibition was more pronounced in the late phase of the EFS-induced relaxation. The inhibitory effect of ODQ on EFS-induced relaxation was not affected by additional application of L-NOARG. When NO-formation was blocked by L-NOARG, a subsequent addition of ODQ gave no further inhibition of the relaxation. These findings suggest that inhibitory non-adrenergic, non-cholinergic neurotransmission in guinea-pig colon is dependent on endogenous formation of NO, and that the NO-effect is exclusively mediated via the soluble guanylyl cyclase pathway. The existence of an NO-independent inhibitory transmission, which is not mediated through the cyclic GMP pathway, is also indicated. Furthermore, it is demonstrated that the NO/soluble guanylyl cyclase-independent transmission has an earlier onset as compared with the NO/soluble guanylyl cyclase-dependent pathway.

Animals↗
PubMed1998

Gadolinium chloride inhibition of pulmonary nitric oxide production and effects on pulmonary circulation in the rabbit.

Nitric oxide is an important regulator of pulmonary vascular resistance. Pulmonary nitric oxide formation is detectable in exhaled air and the synthesis is partly stretch-dependent. Gadolinium chloride (GdCl3) reduces pulmonary nitric oxide formation, possibly by interference with stretch-activated cellular calcium influx, but the effect on pulmonary circulation is not known. We therefore measured exhaled nitric oxide and pulmonary vascular resistance in anaesthetised rabbits, and compared the effects of GdCl3 with those of an nitric oxide-synthase inhibitor (L-N omega-nitro-arginine methyl ester, L-NAME). Both GdCl3 and L-NAME reduced nitric oxide in exhaled air and increased pulmonary vascular resistance. However, the increase in pulmonary vascular resistance was more pronounced with GdCl3 than with L-NAME. A 50% reduction of exhaled nitric oxide caused by either GdCl3 or L-NAME was accompanied by a 90% or 17% increase in pulmonary vascular resistance respectively. Inhaled nitric oxide (40 ppm) reduced pulmonary vascular resistance after L-NAME, but not after GdCl3 infusion. Infusion of glyceryltrinitrate reduced pulmonary vascular resistance after GdCl3 infusion. GdCl3 caused hypoxaemia, probably due to vasoconstriction since lung weight was unaltered. Thus GdCl3 can induce a marked increase in pulmonary vascular resistance, which partly may be caused by inhibition of pulmonary nitric oxide formation. Intact stretch-activated calcium channels may be important for maintenance of normal pulmonary vascular function.

Animals↗
PubMed1997

Blockade of nitric oxide-evoked smooth muscle contractions by an inhibitor of guanylyl cyclase.

Nitric oxide-induced contractile responses of smooth muscle were studied in vitro in guinea-pig small intestine. Application of nitric oxide (NO; 0.3-30 microM) evoked a small initial relaxation followed by a marked contractile response in plexus-containing longitudinal smooth muscle preparations from small intestine. The extent of the NO-evoked contractile response was dose-dependent and the response was blocked by tetrodotoxin. Atropine significantly reduced the NO-evoked contraction and the remaining part was abolished by the NK1-receptor antagonist CP 96,345. An inhibitor of soluble guanylyl cyclase, ODQ (1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one), abolished the NO-evoked contractile response. The results suggest that NO, in addition to the classical direct smooth muscle relaxing effect, causes activation of excitatory neurones, via a pathway utilizing soluble guanylyl cyclase, which leads to a smooth muscle contraction.

Animals↗
PubMed1997

Nerve stimulation-induced nitric oxide release as a consequence of muscarinic M1 receptor activation.

The aim of the present study was to investigate whether nerve stimulation-induced nitric oxide (NO) release in the guinea-pig colon is affected by acetylcholine and to identify the muscarinic receptor subtype involved. Nerve-smooth muscle preparations were suspended in a superfusion chamber and NO/NO2- overflow in the superfusate was detected by chemiluminescence analysis. Transmural nerve stimulation evoked a significant increase in NO/NO2- release, which was inhibited by N(omega)-nitro-L-arginine methyl ester (L-NAME) and abolished by tetrodotoxin. Exogenous acetylcholine concentration-dependently increased NO/NO2- release and atropine reduced nerve stimulation-evoked NO/NO2- release. The muscarinic M1 receptor selective antagonist telenzepine (10(-8) M) was as effective as atropine (10(-6) M) in inhibiting NO/NO2- release. The muscarinic M3 receptor antagonists 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) and para-fluoro-hexahydrosila-difenidol (p-F-HHSiD) markedly inhibited cholinergic contractions at 3 x 10(-8) M and 3 x 10(-7) M respectively, but did not affect NO/NO2- release. In conclusion, nerve-induced NO/NO2- release in the guinea-pig colon is to a substantial part due to muscarinic M1 receptor activation. Thus acetylcholine, a major contractile neurotransmitter in the gut, can release NO which could act as a negative feedback mechanism on intestinal smooth muscle or neuronal activity.

Acetylcholine↗
PubMed1997

Visualisation of nitric oxide released by nerve stimulation.

We have visualised nitric oxide (NO) released from the electrically stimulated myenteric plexus and hypogastric nerve. NO was visualised by a reaction with luminol and hydrogen peroxide to generate photons which were counted using a microscope coupled to a photon counting camera. Electrical stimulation of the tissues induced an increase in photon counts which was frequency-dependent and prevented by inhibition of the NO synthase or by tetrodotoxin. The light emitted during nerve stimulation was not only observed at the nerve terminals but also at the axon and soma. Our results indicate that NO released from the whole nerve cell may affect target cells surrounding all parts of the nitrergic neuron. Thus, NO functions as a unique mechanism of synaptic and non-synaptic communication in the nervous system.

Animals↗
PubMed1997

Nerve-induced release of nitric oxide in the rabbit gastrointestinal tract as measured by in vivo microdialysis.

1. Nitric oxide (NO) has been suggested as a gastrointestinal neurotransmitter, mediating the gastric receptive relaxation and the relaxation in the peristaltic reflex. The aim of the present study was to measure nerve-induced NO formation in vivo in the gastrointestinal tract. 2. Formation of the nitric oxide oxidation products nitrite and nitrate during vagal nerve stimulation were measured in the anaesthetized rabbit. Microdialysis probes were inserted into the wall of the stomach and proximal colon, and nitrite and nitrate in dialysate measured by capillary electrophoresis. 3. During bilateral vagal nerve stimulation there was an increase in nitrite and nitrate formation at the level of the stomach and in nitrite formation at the level of the colon. This increase was inhibited by intravenous administration of the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME 30 mg kg-1). Furthermore, L-NAME significantly increased nerve-induced gastric and colonic contractions, as well as spontaneous colonic contractions. 4. In summary, we present a new methodological procedure for quantification of small changes in nitric oxide formation in vivo. This study provides evidence that nitric oxide is released in the stomach and colonic wall during vagal nerve activity, at concentrations able to cause inhibition of smooth muscle contractions in vivo.

Animals↗
PubMed1997

Inhaled carbon dioxide inhibits lower airway nitric oxide formation in the guinea pig.

The present study addressed the effect of inhaled carbon dioxide on lower airway nitric oxide formation in normoxic anaesthetized guinea pigs. Ventilation with carbon dioxide (1.5, 3, 6, 9 and 12%) induced a concentration-dependent decrease in the basal concentration of nitric oxide in exhaled tracheal air. A maximal reduction in exhaled nitric oxide of approximately 25% was induced by 12% carbon dioxide in inhaled air. Ventilation with positive end-expiratory pressure (7 cmH2O) increased the concentration of exhaled nitric oxide. Inhalation of carbon dioxide had a larger, concentration-dependent, inhibitory effect (maximally 60%) on the lower airway nitric oxide formation induced by ventilation with positive end-expiratory pressure, as compared with the effect on the basal concentration of nitric oxide. The results show that inhaled carbon dioxide suppresses lower airway nitric oxide excretion in the guinea pig. Endogenous carbon dioxide might exert effects through regulation of endogenous nitric oxide formation, for example in the regulation of airway tone or in ventilation-perfusion matching.

Administration, Inhalation↗
PubMed1997

Lung distension and carbon dioxide affect pulmonary nitric oxide formation in the anaesthetized rabbit.

Positive end-exspiratory pressure (PEEP) and nitric oxide (NO) can influence lung VA/Q-matching and pulmonary vascular resistance, and application of PEEP can increase exhaled NO in animals. To obtain a better understanding of these mechanisms, we examined how different types of ventilation or changes in CO2 affect the formation of endogenous NO. Exhaled NO in pentobarbital-anaesthetized rabbits was monitored by chemiluminescence. The animals were enclosed in a chamber and subjected to various modes of positive as well as negative pressure ventilation which was adjusted to induce similar changes in functional residual capacity (FRC) with maintained ventilatory rate and tidal volume. In addition, stepwise increase in FiCO2 (1.0-10%) was studied. Negative extrathoracic end-exspiratory pressure during negative extrathoracic pressure ventilation produced an increase in NO production similar to that of positive end-exspiratory pressure during positive pressure ventilation, the increase consisting of an initial peak followed by a plateau. The faster the FRC was increased, the higher was the initial peak in NO. The greater the increase in FRC, the higher was the plateau NO concentration. Increased FiCO2 caused a dose-dependent reduction in exhaled NO. The observations of lung distension effects on exhaled NO suggest the possibility of stretch receptors or -receptive mechanisms coupled to NO formation within the lung. In addition, NO formation in the lung is influenced by CO2 in a reciprocal fashion.

Anesthesia↗
PubMed1997

Endogenous nitric oxide in the airways of different animal species.

BACKGROUND: High amounts of endogenous nitric oxide (NO) have been demonstrated in the human upper airway, but the role of nasal NO is still unclear. The present study aims to describe nasal NO excretion in different animal species with special living conditions or anatomy. METHODS: Domestic animals (horse, cow, pig, sheep, dog, cat) and zoo-animals (Rhesus monkey, chimpanzee, gorilla, elephant, fur seal, alpaca, yak, dolphin, camel, capybara, bear, tiger, wolf, giraffe, alligator, Harris' hawk, kangaroo) were studied awake, resting or anaesthetised. NO concentrations were measured by chemiluminescence using different analysers and techniques, including measurements on mixed exhaled air, during continuous or intermittent gas sampling, and on single breaths. RESULTS: Rhesus monkeys (number of individuals N = 5) and pigs (N = 2) were compared and displayed quite different excretion patterns. Allowing NO to accumulate in the nose during timed occlusions yielded peak concentrations in monkeys of 0.46 +/- 0.07 parts per million (ppm, mean +/- SEM), 0.59 +/- 0.08 ppm, 0.70 +/- 0.08 ppm and 1.02 +/- 0.05 ppm NO after 15, 30, 60 and 120 s of occlusion. In pigs, 0.012-0.021 ppm NO were recorded, independent of occlusion time. The chimpanzee was similar to the Rhesus monkey and the highest NO value, 2.9 ppm, was recorded after 4-5 min of occlusion. In single breaths from 3 elephants 0.031-0.082 ppm, from 1 gorilla 0.029 ppm, and from 1 chimpanzee 0.069 +/- 0.003 ppm NO (8 observations) were recorded. CONCLUSIONS: We found considerable species difference in nasal NO excretion with pronounced amounts only in primates and elephants. The physiological implications of these findings remain to be defined.

Animals↗
PubMed1997

Stretch-induced stimulation of lower airway nitric oxide formation in the guinea-pig: inhibition by gadolinium chloride.

The effect of stretch on lower airway nitric oxide formation was studied in normoxic tracheostomized anaesthetized guinea-pigs. Increase of level of positive end-expiratory pressure caused increased lower airway nitric oxide formation, as measured by its presence in exhaled tracheal air. The L-type calcium channel blocker, verapamil, did not decrease lower airway nitric oxide formation. Neither the local anaesthetic xylocaine nor the ganglion blocker trimetaphan affected exhaled nitric oxide, excluding local and centrally-mediated neuronal reflexes. Intravenous administration of gadolinium chloride (GdCl3, 50 mg/kg) induced a rapid and pronounced decrease (75%) in the basal level of exhaled nitric oxide. GdCl3 completely abolished lower airway nitric oxide formation induced by ventilation with positive end-expiratory pressure (7 cm H2O). GdCl3 induced hypoxaemia, but there was no indication for the development of lung oedema. The results indicate that positive end-expiratory pressure stimulates lower airway nitric oxide formation in the guinea-pig. GdCl3 inhibits lower airway nitric oxide formation in the guinea-pig in vivo, perhaps by interference with stretch-induced cellular calcium-influx.

Animals↗
PubMed1997

Endogenous nitric oxide in the upper airways of premature and term infants.

Concentrations of endogenous nitric oxide (NO) were measured in premature (n = 18) and term infants (n = 7). Nasal gas was aspirated continuously and after timed occlusions, 15 s and 60 s, by a fast-response chemiluminescence analyser. The sampling flow rate was 20 ml min-1. Typical NO recordings consisted of plateaux and postocclusive peaks. In term infants peak NO concentrations (60 s occlusion) were 2.71 +/- 0.44 parts per million (ppm) within 10 min after birth, increasing (p < 0.05) to 3.81 +/- 0.25 ppm at 4-7 d postnatally. Peak NO values (15 s occlusion) averaged 1.22 +/- 0.16 ppm in premature infants (postconceptional age 25-37 weeks, body weight 623-2844 g) and the NO concentrations increased significantly with postconceptional age (p < 0.05). Nasal excretion rate, estimated from plateau NO concentrations and sampling flow rate, was 0.10 +/- 0.01 nmol min-1 kg-1 in both groups. We conclude that premature and term newborn infants excrete considerable amounts of NO in the upper airways, with hitherto not fully known functions.

Cross-Sectional Studies↗
PubMed1996

Endogenous nitric oxide in the upper airways of healthy newborn infants.

The endogenous production of nitric oxide (NO) in the upper airways was studied in healthy newborn infants within the first minutes after delivery (N = 2) and at postnatal ages of 1 and 24 h (N = 13). Measurements were made in infants born vaginally or by cesarean section and at various times after the rupture of membranes. Gas was sampled from the nose and pharynx, and NO concentrations were determined by a fast response chemiluminescence analyzer. Sampling from the nose at a constant flow of 20 mL/min gave 0.27 +/- 0.01 parts per million (mean +/- SEM, ppm) of NO, independent of age and mode of delivery (vaginal delivery and cesarean section). Allowing NO to accumulate in the nose for 15-120 s yielded peak concentrations up to 4.6 ppm. A 30% increase was noted between 1 and 24 h of age. We conclude that nasal peak NO concentrations in the ppm range can be demonstrated in the healthy newborn infant within the first hour after birth. Consequently autoinhalation of endogenously produced upper airway NO may play a role in the adaptation of the respiratory system to postnatal life in the human.

Female↗
PubMed1995

Rapid tolerance to formation of authentic NO from nitroglycerin in vivo.

Direct evidence for in vivo NO formation from nitroglycerin (GTN) was obtained by measurements of exhaled nitric oxide in anaesthetized. Infusions of GTN (1-100 micrograms kg-1 min-1 i.v.) induced dose-dependent and biphasic increments in exhaled NO parallelled by reductions in systemic blood pressure. The NO detected during GTN infusion was unaffected by the nitric oxide synthase inhibitor L-NAME or acute i.v. administration of L-cysteine, N-acetyl-L-cysteine or glutathione. The present data demonstrate that NO is formed from GTN in vivo, and that tolerance in vivo is due to decreased formation of NO.

Acetylcysteine↗
PubMed1995

Modulation of smooth muscle activity by nitric oxide in the human upper urinary tract.

The aim of the study was to ascertain whether nitric oxide (NO) might regulate motility in the human upper urinary tract. Smooth muscle activity in the human renal pelvis and proximal ureter was studied in vitro in organ baths, and nitric oxide synthase (NOS) activity was studied by measurement of citrulline formation. NO, glyceryl trinitrate (GTN) and sodium nitroprusside (SNP) significantly reduced the frequency of spontaneous rhythmic contractions in renal pelvis and proximal ureter. Exogenously applied NO elicited relaxations in pre-contracted renal pelvis. Calcium-dependent NOS activity was significant in the renal pelvis but undetectable in the ureter. Also, NOS activity was absent in hydronephrotic renal pelvis. NO, SNP and GTN inhibited smooth muscle activity in the human upper urinary tract. NOS activity was obtained in normal renal pelvis but not in hydronephrotic renal pelvis. Regulation of urinary tract NO concentrations might offer a strategy for treatment of renal colic and disturbances in upper urinary tract motility.

Citrulline↗
PubMed1995

Positive end-expiratory pressure ventilation elicits increases in endogenously formed nitric oxide as detected in air exhaled by rabbits.

BACKGROUND: Nitric oxide (NO) formed from L-arginine is exhaled by mammals and regulates pulmonary vascular tone. Little is known about how its formation is stimulated. METHODS: The concentration of NO in exhaled air was monitored by chemiluminescence in pentobarbital-anesthetized rabbits receiving mechanical ventilation by tracheostomy with graded positive end-expiratory pressure (PEEP). RESULTS: Introduction of PEEP (2.5-15 cmH2O) elicited dose-dependent and reproducible increments in exhaled NO and in arterial oxygen tension (PaO2). The increase in exhaled NO exhibited a biphasic pattern, with an initial peak followed by a partial reversal during the 4-min period at each level of PEEP. Thus, at a PEEP of 10 cmH2O, exhaled NO initially increased from 19 +/- 4 to 30 +/- 5 parts per billion (ppb) (P < 0.001, n = 9) and then decreased to 27 +/- 5 ppb (P < 0.005) at the end of the 4-min observation period. Simultaneously, PaO2 increased from 75 +/- 12 mmHg in the control situation to 105 +/- 11 mmHg (P < 0.05) at a PEEP of 10 cmH2O. After bilateral vagotomy, including bilateral transection of the depressor nerves, the increase in exhaled NO in response to PEEP was significantly reduced (P < 0.01). Thus, after vagotomy, a PEEP of 10 cmH2O elicited an increase in the concentration of exhaled NO from 13 +/- 3 to 17 +/- 3 ppb (n = 7). Vagotomy did not affect the baseline concentration of NO in exhaled air. The PEEP-induced increments in PaO2 were not affected by the NO synthase inhibitor L-N omega-arginine-methylester (30 mg.kg-1 intravenously). In open-chest experiments, PEEP (10 cmH2O) induced a reduction in cardiac output from 317 +/- 36 to 235 +/- 30 ml.min-1 and an increase in exhaled NO from 23 +/- 6 to 30 +/- 7 ppb (P < 0.05, n = 5). Reduction in cardiac output from 300 +/- 67 to 223 +/- 52 ml.min-1 by partial obstruction of the pulmonary artery did not significantly increase exhaled NO (from 23 +/- 7 to 25 +/- 6, difference not significant; n = 3). CONCLUSIONS: PEEP elicited increments in exhaled NO, perhaps by a stretch-dependent effect on the respiratory system. This finding may be attributed in part to a vagally influenced mechanism.

Animals↗