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Biomedical subjects

L E Gustafsson

Publications and source records attributed to L E Gustafsson.

At least 73 records · Page 4Linked to original sources
PubMed1993

[Nitric oxide--more than a vasodilator].

Endothelium-dependent vasodilation is mediated by nitric oxide (NO), which is synthesised from the amino acid arginine. The enzymes involved are present in several cell types, and NO has important regulatory functions in many of the organ systems of the body. NO seems to be of importance in the regulation of blood pressure, neuronal activity in the peripheral and central nervous systems, in ventilation perfusion-matching in the lungs, and in immune defense. Although the clinical use of nitroglycerin is more than a century old its mechanism of action, the liberation of NO, has only recently been elucidated. Endogenous nitric oxide synthesis inhibitors have been identified, and both these and NO itself are being examined in clinical trials.

Animals↗
PubMed1993

Release of nitric oxide evoked by nerve stimulation in guinea-pig intestine.

Non-adrenergic non-cholinergic nerves provide the main inhibitory autonomic supply to intestinal smooth muscle and other organ systems. Nitric oxide is likely to act as a neurotransmitter in these nerves and a nitric oxide synthase has been demonstrated in autonomic neurons. However, there are as yet no biochemical measurements of nerve-induced release of nitric oxide or its breakdown products nitrite and nitrate. We have examined the possibility that nitric oxide is released by stimulation of autonomic nerves in the guinea-pig intestine by studying the release of nitric oxide, nitrite and nitrate. The biological activity of a vascular relaxing factor released by the activation of these nerves was compared with that of nitric oxide using a bioassay system as previously described. Nitrite and nitrate release were measured by high-performance liquid chromatography using UV absorbance. The relaxation of the bioassay tissues to nerve stimulation was indistinguishable from the relaxation induced by nitric oxide. Both relaxations were equally unstable and inhibited to a similar degree by haemoglobin and enhanced by superoxide dismutase. Furthermore, the release of the relaxing factor was attenuated by treatment with the nitric oxide synthase inhibitor N omega-nitro-L-arginine. Concomitant with the release of the relaxing factor, which was frequency dependent, there was a frequency-dependent release of nitrite and nitrate in amounts sufficient to explain the vascular relaxations observed during nerve stimulation. The release of nitrite and nitrate was also inhibited by treatment with the nitric oxide synthase inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗
PubMed1993

Near fatal pulmonary hypertension after surgical repair of congenital diaphragmatic hernia. Successful use of inhaled nitric oxide.

The addition of 10-20 parts per million nitric oxide to the inspired gas was successful in controlling near fatal pulmonary hypertension after surgical repair of a congenital diaphragmatic hernia in a neonate. A preceding prostacyclin infusion was unable to prevent the failure of pulmonary perfusion. No side effect of nitric oxide therapy was observed, and ventilatory support could be substantially reduced as a result of the treatment. On the basis of the striking and lifesaving effects of nitric oxide therapy demonstrated in this child, we believe that nitric oxide treatment will prove to be a major contribution to the management of postoperative pulmonary hypertensive crises.

Acidosis↗
PubMed1993

Modulation of cholinergic and substance P-like neurotransmission by nitric oxide in the guinea-pig ileum.

1. The role of endogenous nitric oxide (NO) as a modulator of enteric neurotransmission was investigated in longitudinal muscle myenteric plexus (LMMP) preparations of guinea-pig isolated ileum. 2. In tissues previously incubated with [3H]-choline, exogenous NO inhibited electrically-evoked [3H]-choline overflow as well as responses to exogenous agonists, indicating that NO has the potential of neuromodulation both pre- and postjunctionally. 3. A series of NO synthase inhibitors enhanced contractile responses to nerve stimulation indicating inhibitory neuromodulation by endogenous NO. 4. The potency order of the NO synthase inhibitors and their consistent effects after dexamethasone, on responses to nerve stimulation, indicate action on a constitutive NO synthase. 5. Responses enhanced by NO synthase inhibitors were inhibited by the substance P receptor antagonist, spantide, suggesting a neuromodulatory influence on substance P-like neurotransmission by the endogenous NO. 6. NO synthase inhibition did not modify contractile responses to application of acetylcholine or substance P, or [3H]-choline overflow, indicating that endogenous NO mainly has a prejunctional inhibitory action on substance P-like neurotransmission. Nor did it modify responses to direct electrical muscle stimulation in the presence of tetrodotoxin. This suggests a prejunctional enhancing effect by NO synthesis inhibition. 7. Evidence for endogenous NO modulation of acetylcholine release was obtained when NO synthase inhibition modified atropine-sensitive, nerve-mediated contractile responses. However, [3H]-choline overflow was unaltered by NO synthase inhibition. 8. NO synthase inhibition did not modify responses to inhibitory neurotransmission. 9. The findings suggest that endogenous NO inhibits substance P-like motor neurotransmission, probably via prejunctional mechanisms. Cholinergic transmission may also be reduced by endogenous NO, acting prejunctionally.

Acetylcholine↗
PubMed1993

Allergen-induced airway obstruction in guinea-pigs is associated with changes in nitric oxide levels in exhaled air.

Endogenously produced nitric oxide (NO) was monitored in exhaled air from ovalbumin-sensitized and pentobarbital anaesthetized guinea-pigs. Stable levels of nitric oxide were detected in exhaled air over a 30-min control period in each experiment (9.2 +/- 1.4 parts per billion, [ppb]). Insufflation pressure and NO in exhaled air immediately increased, in a dose dependent manner, in response to challenge with nebulized allergen (Ovalbumin, 0.1-10 mg). Indomethacin (5 mg kg-1) augmented the allergen-induced increases in insufflation pressure and NO. Fifteen min after the challenge the insufflation pressure remained elevated while NO in exhaled air had dropped below control levels. The increase in insufflation pressure induced by inhalation of PGF2 alpha (5 micrograms) was accompanied by an increase in nitric oxide in exhaled air, which however was significantly less than the increase in NO induced by allergen challenge. The results suggest a role for NO mechanisms in asthma.

Animals↗
PubMed1993

Endogenous nitric oxide in single exhalations and the change during exercise.

The concentrations of endogenous nitric oxide (NO) and CO2 were measured in exhaled air from healthy humans. During a single exhalation, NO concentrations peaked when the CO2 level reached its plateau. However, whereas CO2 levels remained at a plateau throughout the exhalation, NO concentrations declined after having peaked. After breathholding (5 to 60 s) NO peaked at a higher level than during normal breathing. Nitric oxide concentrations in exhaled air decreased during physical exercise (50 to 100 W). However, taking the increased ventilatory minute volume into account, excretion of NO markedly increased during exercise. The data are compatible with the hypothesis that the NO detected in exhaled air is formed preferentially in the terminal and respiratory bronchioles, and they suggest increased production of NO into exhaled air during exercise and during hyperventilation at rest.

Adult↗
PubMed1992

Ethanol can inhibit nitric oxide production.

Endogenous nitric oxide (NO) in exhaled air from anaesthetized rabbits was monitored by chemiluminescence. Ethanol (3-30 mmol kg-1) infused i.v. dose dependently reduced the levels of exhaled NO, with an IC50 of 23 +/- 3 mmol kg-1. L-Arginine (1 g kg-1) did not reverse the effect of ethanol. These results demonstrate the inhibition of NO formation by ethanol in vivo.

Animals↗
PubMed1992

Functional and morphological comparisons between cochlear outer hair cells and muscle tissues in the guinea-pig.

The effect of polylysine on the motility of outer hair cells and various muscle types was compared. Poly-L-lysine and its stereoisomer, poly-D-lysine, inhibited acoustically induced length changes of isolated outer hair cells from the guinea-pig hearing organ. The frequency specific displacements of the hearing organ in response to a tone stimulus are also inhibited to polylysine (Brundin et al. 1991). Poly-L-lysine, and its stereoisomer, irreversibly attenuated motile responses to transmural stimulation of guinea-pig ileum, vas deferens and taenia coli in a dose dependent manner, but were without significant effect on motile responses in skeletal and heart muscle. L-lysine, D-lysine, and the negatively charged polyaminoacid poly-L-aspartate, were without significant effect on outer hair cell and smooth muscle motility. The inhibitory effect of polylysine in smooth muscle is a direct effect on the muscle cell since polylysine attenuated acetylcholine- and adenosine triphosphate-induced contractions in the ileum, and ATP- or noradrenaline-induced contractions in the vas deferens. Pillar structures, believed to be of importance to excitation contraction coupling, were compared. In heart and skeletal muscle the pillars span the gap between sarcoplasmic reticulum and T-tubuli, deeply recessed into the muscle cell. In smooth muscle and outer hair cell the pillars are in closer relation to the cell exterior. The length of the pillars of the outer hair cells exceeds by two times that of smooth and skeletal muscle. The susceptibility of outer hair cells and smooth muscle tissue to the positively charged polylysine may indicate similarities in membrane or channel composition.

Animals↗
PubMed1992

Isolated bronchi from asthmatics are hyperresponsive to adenosine, which apparently acts indirectly by liberation of leukotrienes and histamine.

Bronchial hyperresponsiveness can be demonstrated in asthmatic subjects by inhalation of adenosine, but the action of adenosine at the level of the human airway smooth muscle has received comparatively little attention. We have previously observed that bronchi isolated from one asthmatic patient contracted in response to adenosine. We have therefore, during the course of a 3-yr study, further characterized the effects of adenosine in bronchi prepared from surgical specimens of lung tissue of asthmatics and of nonasthmatics. Contraction responses were always studied in vitro the same day the tissues were obtained. Bronchi from asthmatics (19 strips from six patients) were more sensitive to adenosine than were bronchi from nonasthmatics (21 strips, seven patients). In contrast, there was no difference in sensitivity to histamine or leukotriene C4 between the two groups, nor was the maximal tissue contractility different. The contractile effect of adenosine was inhibited by the adenosine A1-antagonist 2-thio-[(1,3-dipropyl)-8-cyclopentyl]-xanthine as well as by the dual A1 and A2 antagonists 8-(p-sulfo)-phenyltheophylline and theophylline. The combination of leukotriene antagonism (receptor-antagonist ICI 198,615 or biosynthesis inhibitor MK-886) and histamine antagonism (antihistamines mepyramine and metiamide) blocked the contractile effects of adenosine, suggesting that adenosine acts indirectly by liberation of leukotrienes and histamine, possibly from mast cells. The findings of increased sensitivity to adenosine in bronchi from asthmatics to our knowledge represents the first evidence of increased bronchial reactivity in vitro in asthmatics.

Adenosine↗
PubMed1991

Endogenous nitric oxide is present in the exhaled air of rabbits, guinea pigs and humans.

The presence of nitric oxide (NO) in the exhaled air of humans and of anaesthetized rabbits and guinea pigs was demonstrated by chemiluminescence, diazotization and mass spectrometry. This NO is endogenously produced in the lung by an NO synthase, since its generation in guinea pigs and rabbits was inhibited by N omega-nitro-L-arginine methyl ester and NG-monomethyl-L-arginine, inhibitors of this enzyme. The effect of the inhibitors was reversed by the precursor of NO synthesis, L-arginine. Since NO is produced by normal vascular endothelium for the physiological regulation of blood flow and pressure and also by activated macrophages to contribute to non-specific immunity, our experiments suggest that NO may play both vascular regulatory and host defence roles in pulmonary physiology and pathophysiology.

Amino Acid Oxidoreductases↗
PubMed1991

Nerve-induced tachykinin-mediated vasodilation in skeletal muscle is dependent on nitric oxide formation.

Nerve-induced vasodilatation was studied by intravital microscopy of the rabbit tenuissimus muscle, pretreated with pancuronium, phentolamine, and guanethidine. Nerve stimulation of the tenuissimus nerve induced a vasodilatation which was frequency and pulse duration-dependent and insensitive to atropine and propanolol but abolished by tetrodotoxin. The nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME, 100 microM), but not its enantiomer, D-NAME, markedly inhibited the vasodilation induced by nerve stimulation or by exogenous substance P or neurokinin A. Vasodilatation due to calcitonin gene-related peptide, prostaglandin E2 or nitroprusside was unaffected. The substance P antagonist, spantide (30 microM), significantly attenuated nerve-induced vasodilatation, in parallel with L-NAME. Our results indicate that nerve-induced vasodilatation in skeletal muscle can be attributed to the release of substance P and/or other tachykinins and that nitric oxide subsequently mediates the response to endogenous tachykinins released from nerves.

Animals↗
PubMed1991

Modulation of neuroeffector transmission in the guinea pig pulmonary artery by endogenous nitric oxide.

The influence of endogenous nitric oxide (NO) on neuroeffector transmission in segments of guinea pig pulmonary artery was analyzed by application of NG-monomethyl-L-arginine (L-NMMA). L-NMMA enhanced contractile responses to nerve stimulation and this enhancement was counteracted by L-arginine. The enhancement remained after removal of the endothelium. L-NMMA enhanced contractions to exogenous noradrenaline. After blockade of adrenergic transmission by phentolamine, L-NMMA enhanced contractions induced by nonadrenergic-noncholinergic (NANC) neurotransmission. Stimulation-induced release of [3H]noradrenaline was unchanged by L-NMMA. The results suggest that endogenous NO exerts a postjunctional inhibition on adrenergic neurotransmission in the guinea pig pulmonary artery. A concomitant pre- and/or postjunctional inhibition of NANC transmission is implicated. The neuromodulation by NO does not require an intact endothelium.

Animals↗
PubMed1991

Role of adenosine in functional hyperemia in skeletal muscle as indicated by pharmacological tools.

The hypothesis that adenosine mediates blood flow increments in contracting skeletal muscle was evaluated by intravital microscopy of the microcirculation in the tenuissimus muscle of anesthetized rabbits. Motor nerve stimulation elicited muscle contractions and frequency-dependent arteriolar dilatation, particularly in terminal arterioles. The pulse duration (0.05 ms) and voltage (1.5-5 V) precluded activation of vasoconstrictor fibers, as also indicated by the lack of effect of phentolamine on resting vascular tone and on the hyperemic response to nerve stimulation. The specific adenosine receptor antagonist, 1,3-dipropyl-8-p-sulfo-phenylxanthine (DPSPX; 10(-5) M), attenuated the hyperemic response to muscle contractions. The adenosine uptake inhibitor dipyridamole (10(-8)-10(-6) M) dose-dependently dilated microvessels, an effect prevented by DPSPX (10(-5) M). Moreover, dipyridamole (10(-7) M) augmented contraction-induced hyperemia. The enhancement by dipyridamole was reversed by DPSPX (10(-5) M). The effects of adenosine uptake inhibitor and antagonist were invariably more marked in terminal than in transverse arterioles, and also more pronounced at higher stimulation frequencies. Motor nerve stimulation failed to induce alterations in vascular diameters when the neuromuscular junction was blocked by pancuronium. Thus, our observations indicate that functional hyperemia after motor nerve-induced contractions of the skeletal muscle was of postjunctional origin. Apparently, activation of adenosine receptors was responsible for a part of the evoked vasodilation.

Adenosine↗
PubMed1991

Endothelin modulation of neuroeffector transmission in smooth muscle.

In a series of muscle preparations, the peptides endothelin-1 (ET-1) and endothelin-3 (ET-3) were investigated for effects on basal muscle tone, responses to transmural nerve stimulation, and release of [3H]norepinephrine or [3H]acetylcholine. ET-1 and ET-3 contracted rat vas deferens and guinea pig ileum, ET-1 being the most potent. In the guinea pig taenia coli, ET-1 induced a relaxation whereas ET-3 was almost without relaxing effect. In the rat vas deferens, ET-1 and ET-3 enhanced contractile responses to nerve stimulation, whereas the nerve-induced release of [3H]norepinephrine was inhibited by ET-1 but not by ET-3. Contractions to exogenous ATP were increased by ET-1 whereas contractions to norepinephrine were not. In the guinea pig ileum, nerve-induced contractions were inhibited by ET-1 and ET-3 as was acetylcholine release, whereas contractions to exogenous acetylcholine were enhanced by ET-1. The inhibition of nerve-induced contractions by the endothelins was not affected by treatment with 8-(p-sulfophenyl)theophylline, BW755C, or indomethacin. The relaxation by ET-1 in the guinea pig taenia coli was not affected by treatment with NG-monomethyl-L-arginine, BW755C, or indomethacin. In conclusion, ET-1 exerted a stimulatory postjunctional effect and concomitantly an inhibitory prejunctional effect on adrenergic and cholinergic neurotransmission. Also, ET-3 exerted a stimulatory postjunctional effect, whereas a prejunctional inhibitory effect of ET-3 only was evident on cholinergic neurotransmission. Blockade of the production of nitric oxide or arachidonic acid metabolites or application of an adenosine antagonist did not alter the effects of ET-1 or ET-3.

Acetylcholine↗
PubMed1991

Nitric oxide requirement for vasomotor nerve-induced vasodilatation and modulation of resting blood flow in muscle microcirculation.

Intravital microscopy of rabbit tenuissimus muscle was used for studies of endogenous nitric oxide as a microvascular regulator in vivo. Derivatives of arginine were administered in order to modulate the formation of nitric oxide from L-arginine. N omega-nitro-L-arginine methylester (L-NAME) (1-100 mg kg-1 i.v.) dose-dependently reduced microvascular diameters. A concomitant blood pressure increase and a decrease in heart rate was observed. The blood pressure increase induced by L-NAME (30 mg kg-1) was reversed by L-arginine (1 g kg-1) but not D-arginine. Vasodilation in response to topical acetylcholine (0.03-3 microM) was significantly inhibited by L-NAME (30 mg kg-1), whereas vasodilation by sodium nitroprusside (300 nM) was not affected. Vasomotor nerve-induced vasodilatation, induced by stimulation of the tenuissimus nerve after neuromuscular blockade by pancuronium in animals pretreated with guanethidine, was significantly attenuated by L-NAME, an effect also reversed by L-arginine. The vasodilatation in response to active contractions of the muscle induced by motor nerve stimulation as well as the vasodilator response elicited by graded perfusion pressure reductions were unaffected by L-NAME or NG-monomethyl-L-arginine (L-NMMA, 10(-4) M) administered topically. Our results indicate that endogenous nitric oxide formed from L-arginine is a modulator of microvascular tone in vivo. Furthermore, the results suggest that endogenous nitric oxide is required for vasomotor nerve-induced vasodilatation, whereas it does not appear to play a role in myogenic vasodilatation or functional hyperaemia in this tissue.

Animals↗