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Biomedical subjects

K Alving

Publications and source records attributed to K Alving.

104 records · Page 6Linked to original sources
PubMed1990

Innervation of lower airways and neuropeptide effects on bronchial and vascular tone in the pig.

The occurrence and distribution of peptide-containing nerve fibres [substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), neuropeptide Y (NPY)] and noradrenergic nerve fibres [tyrosine hydroxylase (TH)- and dopamine beta hydroxylase (DBH)-positive] in the airways of the pig were studied by means of immunohistochemistry. SP- and CGRP-immunoreactive (-IR) nerve fibres were present close to and within the lining respiratory epithelium, around blood vessels, within the tracheobronchial smooth muscle layer and around local tracheobronchial ganglion cells. The content of CGRP- and neurokinin A (NKA)-like immunoreactivity (-LI) measured by radioimmunoassay (RIA) was twice as high in the trachea compared to that in the peripheral bronchi. SP was a more potent constrictor agent than NKA on pig bronchi in vitro. CGRP had a relaxant effect on precontracted pig bronchi. On blood vessels CGRP exerted a relaxant effect that was more pronounced on pulmonary arteries than on bronchial arteries. VIP/PHI-IR fibres were seen in association with exocrine glands and in the tracheobronchial smooth muscle layer. VIP-positive nerve fibres were abundant around blood vessels in the trachea but sparse or absent around blood vessels in the peripheral bronchi. This histological finding was supported by RIA; it was shown that the content of peptides displaying VIP-like immunoreactivity (-LI) was 18 times higher in the trachea compared to peripheral bronchi. VIP was equally potent as CGRP in relaxing precontracted pig bronchi in vitro. Both bronchial and pulmonary arteries were relaxed by VIP. NPY was colocalized with VIP in tracheal periglandular nerve fibres and in nerve fibres within the tracheobronchial smooth muscle layer. NPY was also present in noradrenergic (DBH-positive) vascular nerve fibres. The content of NPY was much higher (15-fold) in the trachea compared to small bronchi. NPY caused a contraction of both pulmonary and bronchial arteries. The bronchial smooth muscle contraction to field stimulation in vitro was purely cholinergic. A noncholinergic relaxatory effect following field stimulation was observed after bronchial precontraction. Capsaicin had no effect on pig bronchi in vitro.

Animals↗
PubMed1990

Peptidergic innervation of rat lymphoid tissue and lung: relation to mast cells and sensitivity to capsaicin and immunization.

The peptidergic innervation of lymphoid tissue and the lung in relation to mast cells was studied in rat. The sensitivity of neuropeptide-containing nerves to capsaicin treatment and immunization was also examined. Measurements of the content of neurokinin A and calcitonin gene-related peptide revealed that the lung contained the highest content of both neuropeptides; lymph nodes had intermediate levels, whereas the spleen had the lowest content. Immunohistochemistry showed that the calcitonin gene-related peptide- and neurokinin A-immunoreactive nerves in lymph nodes were mainly found around blood vessels, whereas in the lung the nerves were present within the lining respiratory epithelium, bronchial smooth muscle, around blood vessels and close to lymphoid aggregates. Combined immunohistochemistry for serotonin (5-hydroxytryptamine), as a marker for mast cells, and tachykinins or calcitonin gene-related peptide revealed that a close association was often present between the nerves and 5-hydroxytryptamine-positive cells in the bronchi of the lung, while 5-hydroxytryptamine-positive cells were not observed in lymph nodes. The neurokinin A and calcitonin gene-related peptide content in lymph nodes, spleen and lung, but not the content of neuropeptide Y, was markedly decreased by capsaicin treatment, suggesting a sensory origin for the two former peptides. Aerosol immunization increased the levels of calcitonin gene-related peptide in the lung, whereas the content in mediastinal lymph nodes was not affected. These data demonstrate a peptidergic innervation mainly of blood vessels in lymphoid tissue and a close relation between sensory nerves and mast cells as well as lymphoid aggregates in the bronchi of the lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Cigarette smoke, nicotine and capsaicin aerosol-induced vasodilatation in pig respiratory mucosa.

1. Anesthetized pigs were used to study vascular responses in the sphenopalatine artery (SPA), superior laryngeal artery (SLA) and bronchial artery (BA) upon exposure to cigarette smoke or aerosol of nicotine and capsaicin. Direct blood flow recordings were made with ultrasonic probes around the vessels. 2. Smoke from one cigarette was administered as inhalation for 2 min with or without a Cambridge filter which removes the particulate matter including nicotine from the smoke. Aerosols of nicotine (2.5 mg) or capsaicin (10 mg) were administered to the nose or the lower airways for 3 min. 3. Cigarette smoke exposure caused a reproducible reduction of the vascular resistance (VR) suggesting vasodilatation in the SPA, SLA, and especially the BA. The vasodilatation was not modified by the Cambridge filter, suggesting that it was caused by vapour phase components rather than nicotine. 4. The smoke effect was not changed after pretreatment with the cyclo-oxygenase inhibitor, diclofenac, or with atropine, guanethidine, H1- or H2-histamine receptor antagonists, nedocromil, or by vagotomy. The smoke-evoked decrease in VR was not modified by the nicotinic receptor antagonist chlorisondamine in the SLA or BA. 5. In pigs pretreated with increasing doses of capsaicin two days earlier, the decrease in VR upon smoke exposure in both the BA and SLA was unaffected while the change in VR was attenuated in the SPA. 6. Nicotine aerosol had no effect on VR in the peripheral airways supplied by the BA while a decrease in VR was observed in the SLA and SPA. The nicotine response was reduced after capsaicin pretreatment in the nasal and upper tracheal circulation. 7. Capsaicin aerosol reduced VR in the vascular beds supplied by the SPA, SLA and BA and this response was markedly reduced after capsaicin pretreatment. 8. The mechanisms underlying vasodilatation upon cigarette smoke exposure in the bronchial mucosa are at the moment unclear while both non-cholinergic parasympathetic and sensory components may be involved in the nose. Capsaicin induced a vasodilatation at all levels via sensory mechanisms, whereas nicotine-evoked vasodilatation is restricted to the upper airway mucosa and is at least partly dependent on parasympathetic reflexes involving capsaicin-sensitive sensory nerves.

Aerosols↗
PubMed1990

Capsaicin and histamine antagonist-sensitive mechanisms in the immediate allergic reaction of pig airways.

The airway vascular and bronchial responses were studied in pigs sensitized with Ascaris suum. Ascaris, histamine (H) and capsaicin aerosol all induced a clear-cut increase in blood flow in the nasal, laryngeal and bronchial circulation with a decrease in vascular resistance of 20-40%. When delivered to the lung both ascaris and histamine, but not capsaicin, caused pulmonary airflow obstruction with increase in resistance and a fall in dynamic compliance of 40-70%. After pretreatment of pigs with a combination of the H1- and H2-receptor antagonists terfenadine and cimetidine, the vascular and bronchial responses were strongly reduced to both histamine (by greater than 77%) and ascaris (by greater than 58%), but not to capsaicin aerosol. The bronchoconstriction to histamine was found to be mediated by H1-receptors only, while both H1- and H2-antagonists were necessary to block the vasodilatory response, with H2-receptors being more important in the bronchial circulation and H1-receptors being more important in the laryngeal and nasal circulation. Furthermore, when pigs were pretreated with capsaicin systemically 2 days before the experiment, the vasodilation was decreased upon capsaicin (by 80%), ascaris (by greater than 40%) and histamine (by greater than 50%) aerosol challenge. When histamine was administered intravenously the desensitizing effect of capsaicin pretreatment was much less pronounced. The effect of capsaicin desensitization on the pulmonary obstruction upon ascaris and histamine challenge was limited to a 60% reduction of the fall in dynamic compliance and a delayed peak in resistance upon ascaris challenge. We conclude that histamine is one of the main vasodilatory mediators released upon allergen challenge at three different levels of the pig airways. A considerable part of the histamine effect is indirect and probably due to activation of capsaicin-sensitive sensory nerves.

Airway Obstruction↗
PubMed1990

Local and central reflex mechanisms in the neural control of airway microcirculation.

Sensory and parasympathetic neural mechanisms play an essential role in the control of the microcirculation in the airway mucosa in response to inhalation of irritants and in local allergic reactions. Thus extravasation of plasma proteins is evoked by local release of peptides such as substance P (SP) from capsaicin-sensitive sensory nerves upon inhalation of cigarette smoke. Calcitonin gene-related peptide (CGRP) is another vasodilator agent which is also released from airway afferent nerves by capsaicin or antidromic nerve stimulation. Parasympathetic cholinergic and noncholinergic vasodilator mechanisms dominate in the nasal mucosa and trachea whereas the bronchial circulation is influenced mainly by local mechanisms involving mediator release from capsaicin-sensitive sensory nerves. The allergen-induced vasodilatation in the airway mucosa seems to a large extent to be caused by histamine which activates capsaicin-sensitive afferent nerves and evokes peptide release.

Animals↗
PubMed1989

Vagal vasodilatory mechanisms in the pig bronchial circulation preferentially involves sensory nerves.

The present study shows that in contrast to the upper trachea, where the parasympathetic vasodilatory components of both cholinergic and non-cholinergic nature are dominating, the vagal blood flow regulation in the peripheral airways of the pig supplied by the bronchial artery is entirely carried out by local release of vasodilatory mediators from capsaicin-sensitive sensory nerves. Also inhalation of the vapour phase from the major airway irritant cigarette smoke was associated with a marked increase in bronchial blood flow possibly via local axon reflexes. Capsaicin, substance P (SP) and calcitonin gene-related peptide (CGRP) caused vasodilatation in both the trachea and bronchi while vasoactive intestinal polypeptide (VIP) was most active in the trachea. These functional data were supported by immunohistochemical studies showing the presence of SP- and CGRP-containing nerves of presumably sensory origin around bronchial blood vessels while VIP-positive perivascular fibres of local parasympathetic origin were found mainly in the trachea.

Animals↗
PubMed1989

Effects of neuropeptides and capsaicin on tracheobronchial blood flow of the pig.

Blood flow changes upon systemic i.v. injections in the pig of various neuropeptides, capsaicin, bradykinin and histamine were directly monitored by a Transonic blood flowmeter in the superior laryngeal, bronchial and femoral arteries and indirectly in the larynx and skin using laser Doppler flowmetry. To minimize influence of compensatory reflexes and indirect effects, the pigs were pre-treated with atropine, guanethidine, chlorisondamine and capsaicin. Substance P (SP), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), calcitonin gene-related peptide (CGRP), capsaicin, bradykinin and histamine all decreased vascular resistance, suggesting vasodilation in the superior laryngeal and bronchial arteries. All peptides and histamine when given i.v. exerted vasodilatory effects independent of autonomic motor nerves and capsaicin-sensitive afferents. SP was the most potent vasodilator agent tested in both tracheal and bronchial circulation, being about 1000-fold more active than histamine. VIP was about 10-fold more potent than PHI in decreasing vascular resistance and had a preferential action on the SLA compared to CGRP. In the femoral artery capsaicin and also SP in the highest dose increased vascular resistance. Capsaicin increased the laser Doppler signal in both laryngeal mucosa and skin, while i.v. peptides caused variable effects. In conclusion, SP and CGRP mimicked capsaicin-induced vasodilation in the tracheobronchial circulation while VIP had a preferential effect on the tracheal circulation.

Animals↗
PubMed1989

Vagally mediated vasodilatation by motor and sensory nerves in the tracheal and bronchial circulation of the pig.

A new in vivo model is described in which anaesthetized pigs were used to study vascular responses in the bronchial, upper tracheal and laryngeal circulation upon electrical stimulation of the vagal or superior laryngeal nerves. Vagal or superior laryngeal nerve stimulation increased blood flow in the bronchial artery and the superior laryngeal artery, respectively. After pre-treatment with atropine the vasodilatory response in the bronchial artery upon stimulation was not modified while the increase in blood flow in the superior laryngeal artery was reduced. The ganglionic blocking agent chlorisondamine further reduced the nerve stimulation evoked decrease in vascular resistance in the superior laryngeal artery, but did not influence the response of the bronchial artery. Capsaicin induced a marked increase in blood flow both in the bronchial and superior laryngeal arteries after pre-treatment with atropine, guanethidine and chlorisondamine. After capsaicin tachyphylaxis, the vasodilatation upon nerve stimulation in the bronchial artery and the smaller remaining decrease in vascular resistance in the superior laryngeal artery were strongly reduced. Thus, antidromic stimulation of afferent C fibres may increase blood flow via release of vasodilatory peptides such as tachykinins and calcitonin gene-related peptide. The present findings show that local blood flow in the larynx and upper trachea is regulated by cholinergic and non-cholinergic parasympathetic mechanisms and a small capsaicin sensitive, sensory component. On the other hand, the vagal control of the bronchial circulation seems to exclusively involve capsaicin sensitive sensory nerves.

Animals↗
PubMed1989

Effect of neonatal or later capsaicin treatment on bronchial reactivity in sensitized rats. Relation to humoral changes.

Treatment of ovalbumin-sensitized rats with capsaicin resulted in altered bronchial reactivity to both ovalbumin and serotonin. The increase in bronchial reactivity to ovalbumin in neonatally capsaicin-treated rats compared to animals only sensitized may be influenced by the changed ratios of IgA, IgE, and IgG antibodies, together with the inflammation in the lung. Thus, capsaicin given neonatally inhibited the formation of antibodies, both specific titers and total levels, in bronchial lavage.

Age Factors↗
PubMed1987

Effect of capsaicin on bronchial reactivity and inflammation in sensitized adult rats.

The involvement of tachykinins in the airway reactivity of ovalbumin (OA)-sensitized rats was studied by capsaicin (CAPS) treatment. In subcutaneously sensitized animals, the reactivity to both OA aerosol and serotonin given intravenously was decreased when CAPS was given after the sensitization period. No effects on the serum IgE and IgG antibody levels were seen in these animals. In contrast, when CAPS was given before the sensitization period, no effects were seen on the OA aerosol and serotonin reactivities. Immunohistochemical examination revealed that the Ia antigen expression in the bronchial epithelium was increased by both subcutaneous and aerosol sensitization. The CAPS treatment decreased this Ia antigen expression. Histological examination of mononuclear cells, mast cells and goblet cells revealed only small effects on the cell numbers by both the OA sensitization and the CAPS treatment. The results demonstrate a link between tachykinins, serotonin, the immune system and clinical lung reactivity. The mechanisms for this seem to be complex, since the timing of the CAPS treatment and antigen sensitization is crucial for the outcome.

Animals↗
PubMed1986

Antigen-specific down-regulation of bronchial reactivity in rats sensitized daily without adjuvant.

Daily sensitization with ovalbumin (OA) and dog serum albumin (DSA) without adjuvant was performed in rats for 2-week periods. When the antigen was administered subcutaneously (s.c.), antibody responses were induced, as assessed in serum and bronchial lavage, and strong increases in transpulmonary pressure (TPP) after intravenous (i.v.) challenge with antigen. Sensitization without adjuvant with antigen as aerosol for similar periods also evoked pronounced antibody formation, although only weak increases of TPP were seen after challenge. Animals sensitized s.c. with OA and simultaneously exposed to OA as aerosol exhibited suppression of the TPP increase after challenge, whereas the antibody responses were not affected to any great extent. In contrast, the increase of TPP after challenge in animals similarly sensitized s.c. with DSA were not suppressed by OA given simultaneously as aerosol or vice versa.

Adjuvants, Immunologic↗
PubMed1986

Enhancement of the bronchial reactivity in immunized rats by neonatal treatment with capsaicin.

Rats were injected with capsaicin at 1-2 days of age to abolish the content of substance P (SP) in nerve terminals. At 6 weeks of age the capsaicin-treated and control rats were sensitized daily for 1 or 2 subsequent weeks Monday through Friday with ovalbumin (OA). The OA was given without adjuvant as 300 ng subcutaneous (s.c.) injections in the neck region or as 1% aerosol for 30 min. The capsaicin-treated animals which were sensitized s.c. for 2 weeks reacted moderately with increased transpulmonary pressure (TPP) to airway challenge with OA, and strongly to intravenous (i.v.) challenge with OA or serotonin. The capsaicin-untreated animals, which were sensitized with OA, reacted weakly to the challenge. In the challenge. In the animals sensitized with aerosolized OA, slightly lower reactivity was seen compared with those sensitized s.c. Untreated and unsensitized control rats reacted only to serotonin challenge. No animal had any detectable serum or bronchial IgE antibodies. Aerosol-sensitized animals had IgG antibodies in both serum and bronchial lavage. Histologically, the animals treated with capsaicin in contrast to the untreated controls demonstrated a pronounced increase of lymphoid tissue around their bronchi. Their mast cell numbers were increased around vessels and in the pleura and their mucous cell numbers were increased in the epithelium of the bronchi and bronchioli. The sensitization did not add much to this histological picture.

Animals↗
PubMed1985

Immune stimulated regional inflammatory responses mediating lung reactivity in rats.

Daily sensitization of SPF BNxWi/Fu rats with ovalbumin (OA) in aerosol during 2-week periods with a 4-week interval resulted after 7 weeks in IgE, IgA and IgG antibodies in serum and bronchial fluid. After cultivation of the regional, axillary, brachial and mediastinal (ABM) lymph node cells, IgE antibodies were found in the culture supernatant. Such antibodies were not found in culture supernatants of spleen and inguinal lymph nodes. Regional formation of IgE antibodies was also noted in the ABM lymph node cell culture supernatants after subcutaneous (s.c.) injections of 100 ng OA in the neck region. When the injections were given in the tail-root region, the inguinal but not the ABM lymph nodes produced the IgE antibodies. The s.c. sensitization induced inconsistent and rather low IgG and no IgA antibody responses. The aerosol but not the s.c. sensitization induced accumulations of mononuclear cells and mucous cells in the lungs. Clinically, the rats sensitized s.c. in the neck region reacted to aerosol and intravenous (i.v.) challenge as early as 1 week after sensitization had started, whereas the animals sensitized in the tail-root regions reacted 7 and 8 weeks after repeated sensitization. The animals sensitized by aerosol showed only weak clinical reactivity after i.v. challenge.

Animals↗