Search PubMed⌕ Search

Biomedical subjects

K Alving

Publications and source records attributed to K Alving.

At least 91 records · Page 5Linked to original sources
PubMed1993

Pulmonary effects of endogenous and exogenous nitric oxide in the pig: relation to cigarette smoke inhalation.

1. Pentobarbitone-anaesthetized pigs were challenged with cigarette smoke (unfiltered or filtered through a Cambridge glass fibre filter to remove the particulate phase including nicotine), as well as nicotine aerosol and the gas phase components nitric oxide (NO) and carbon monoxide (CO); the effects on the bronchial and pulmonary circulations, and pulmonary airway mechanics, were examined. The relative importance of endogenous NO mechanisms in the pig lung was also studied by giving the NO synthesis inhibitor NG-nitro-L-arginine (L-NOARG; 50 mg kg-1) intravenously. Mean arterial pressure and blood flow in the bronchial, pulmonary and femoral circulations were measured, the latter with ultrasonic flow probes around the supplying arteries, and vascular resistance (VR) was calculated. Changes in pulmonary airways resistance (Rpulm) and lung dynamic compliance (Cdyn) were also determined. Finally, the concentration of NO in inhaled air during cigarette smoke and NO gas challenges was continuously monitored by a chemiluminescence method and the relative contribution of NO in cigarette smoke-induced vascular effects in the pig lung was calculated. 2. Cigarette smoke challenge, with or without a Cambridge filter, caused a rapid vasodilator response in the bronchial circulation and the major part (75%) of this response was probably caused by NO present in smoke. NO challenge caused profound bronchial vasodilation with dose-response characteristics between 10 and 100 p.p.m. The small part of the cigarette smoke-induced response not explained by the NO content may be caused by CO, showing weak vasodilator effect in the bronchial circulation. The L-NOARG-induced relative increase in bronchial VR was 2-3 times higher than the changes in pulmonary, femoral and systemic VR, suggesting a strong influence of endothelial NO mechanisms on basal tone in the bronchial circulation.3. Challenge with unfiltered cigarette smoke induced variable responses in the pulmonary circulation,whereas inhalation of filtered smoke caused consistent pulmonary vasodilatation. The major part of this vasodilator response was probably caused by NO, which was a potent dilator of the pulmonary circulation with maximal effect achieved with as little as 10 p.p.m. The effect of NO may be opposed in unfiltered smoke by the particulate phase (but not nicotine), presumably by inducing sympathetic reflexes. L-NOARG caused similar relative increases in pulmonary, femoral and systemic VR.4. Cigarette smoke inhalation induced bronchodilatation in the pentobarbitone-anaesthetized pig as revealed by changes in Rpulm and Cdyn. Both NO and nicotine may contribute to this response. NO inhalation reduced Rpulm in the basal state with maximal effect at 30 p.p.m. The mechanism for NO-induced bronchodilatation may be indirect in the pig, since pretreatment with L-NOARG blocked the response. L-NOARG did not affect basal Rpulm.5. In conclusion, bronchial vasodilatation caused by continuous cigarette smoke inhalation in the pig,seems to be largely mediated (approximately 75%) by NO. The remaining part could be mediated by CO. Cigarette smoke particles, but not nicotine, may counteract NO-induced relaxation in the pulmonary circulation, thus resulting in variable effects in the pulmonary circulation during challenge with unfiltered cigarette smoke. NO also acts as a bronchodilator in the pig, but the mechanism may be indirect. Finally, endogenous NO mechanisms appear to be strongly involved in the control of basal tone in the bronchial circulation, less so in the pulmonary circulation and not at all in bronchial smooth muscle.

Animals↗
PubMed1993

The ability of ruthenium red to reduce the autonomic reflexes and peptide release evoked by capsaicin administration in the pig in vivo.

In the present study we have investigated the cardiovascular effects and peptide-releasing actions of different capsaicin doses in the absence and presence of the inhibitor of Ca2+ fluxes, ruthenium red, in the pig in vivo. Bolus injections of capsaicin (10, 100 and 1000 micrograms kg-1 i.v.) evoked a concentration-dependent increase in mean arterial pressure and heart rate (HR), while in the bronchial and nasal circulations, a fall in vascular resistance was observed. At the highest capsaicin dose used, there was, in addition, a marked increase in arterial levels of calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-like immunoreactivity (LI). Ruthenium red (RR) significantly reduced the CGRP-LI release, but not the outflow of NPY-LI, at the highest dose of capsaicin as well as the functional effects evoked by low dose capsaicin administration. The inhibitory effects of RR were reversible, i.e. 30 min after ruthenium red administration, bolus injections of capsaicin (10 and 100 micrograms kg-1) induced responses similar to those seen in controls. It is concluded that capsaicin given intravenously to the pig produces profound haemodynamic effects and release of CGRP- and NPY-LI through direct activation of a population of C-fibre endings and increased autonomic discharge. RR inhibits not only the local peptide-releasing properties of capsaicin, but also the centrally directed discharge activity leading to reflex responses, with the latter being less sensitive to RR.

Anesthesia↗
PubMed1993

Increased amount of nitric oxide in exhaled air of asthmatics.

The presence of nitric oxide (NO) in the exhaled air of humans has recently been described. We wanted to assess at what level exhaled NO originates in normal airways, and to determine whether airway inflammation induces changes in the levels of exhaled NO. Exhaled NO was continuously measured by chemiluminescence technique during normal tidal breathing through the nose or mouth, with a detection limit of 1 part per billion (ppb). Twelve control subjects were compared to eight patients with mild atopic asthma and rhinitis caused by occupational allergen. In control subjects, the major part of NO in exhaled air (up to 30 ppb) seemed to originate in the nasal airways, with only minor contribution from the lower airways and the oral cavity. However, in mild asthmatics, the level of exhaled NO during oral breathing, indicating the involvement of the lower airways, was increased 2-3 fold. Since increased production of NO in the lower airways may involve activated macrophages or neutrophils, we suggest that exhaled NO may be used to instantly monitor ongoing bronchial inflammation, at least when involving inducible NO synthase.

Adult↗
PubMed1992

Release of calcitonin gene-related peptide from sensory neurons.

CGRP is released from capsaicin-sensitive sensory neurons in a Ca(2+)-dependent manner in a variety of peripheral organs as well as from central terminals. The mechanisms for CGRP release by low concentrations of capsaicin, electrical antidromic nerve stimulation, and bradykinin have several similar characteristics regarding sensitivity to TTX, CTX, and alpha 2-adrenoceptor activation. High capsaicin concentration and nicotine evoke CGRP release via other mechanisms. The effects of capsaicin, resiniferatoxin, and SO2 are blocked by RR, which probably inhibits ion fluxes associated with capsaicin receptor activation. CGRP released upon irritation of peripheral branches of primary afferents may evoke a variety of cardiovascular actions and influence motility in the gastrointestinal and urogenital tracts.

Animals↗
PubMed1991

Capsaicin-induced local effector responses, autonomic reflexes and sensory neuropeptide depletion in the pig.

Systemic capsaicin pretreatment (total cumulative dose 50 mg/kg administered s.c. over 2h) was performed in pigs under pentobarbitone anaesthesia and the effects on sensory and sympatho-adrenal mechanisms were examined acutely and 2 days after treatment. During pretreatment with capsaicin, pronounced sensory and sympatho-adrenal activation were noticed. This resulted in a several-fold increase in the systemic arterial plasma levels of calcitonin gene-related peptide (CGRP), neurokinin A (NKA), noradrenaline (NA), adrenaline (Adr) and neuropeptide Y (NPY), and a slight increase (39%) in plasma cortisol. Simultaneously, there was marked tachycardia, an increase in blood pressure, total skin erythema and some bronchoconstriction, all lasting for about 30 min. Upon repeated injections tachyphylaxis was observed. 2 days after capsaicin pretreatment, basal plasma levels of the neuropeptides, catecholamines and cortisol as well as basal cardiovascular and pulmonary parameters were similar in control and capsaicin-treated pigs. The tissue content of CGRP and NKA was reduced by 50-65% in the airways and by 80-90% in the skin 2 days after capsaicin pretreatment. In contrast, the CGRP content was unchanged or increased (by 195%) in the nodose and spinal ganglia, respectively. The corresponding tissue levels of vasoactive intestinal polypeptide (VIP) and NPY were basically unchanged in capsaicin-treated pigs. A bolus injection of capsaicin (1 mg/kg i.v.) in control animals resulted in a marked increase in plasma catecholamines and NPY, concomitant with elevation in blood pressure and heart rate. These effects were preceded by an initial bradycardia and decrease in blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Association between histamine-containing mast cells and sensory nerves in the skin and airways of control and capsaicin-treated pigs.

The association between mast cells (visualized by routine staining and immunohistochemistry for histamine) and capsaicin-sensitive nerves (containing calcitonin gene-related peptide (CGRP) and substance P (SP] was studied in the pig. In the 1-ethyl-3(3-diethylaminopropyl)carbodiimide (EDCDI)-fixed skin tissue, histamine-containing mast cells and CGRP/SP-positive nerves were found in close association around blood vessels. In the EDCDI-fixed airway mucosa, only single histamine-containing mast cells were detected. However, many alcian blue-positive mast cells were found, sometimes close to the airway epithelium where CGRP SP-containing nerve were abundant. The CGRP/SP-containing nerve fibres were absent 2 days after systemic capsaicin pretreatment, but no changes in the number and distribution of tissue mast cells, granulocytes or lymphocytes, or the number of blood leukocytes were detected. Local injection of allergen, histamine and capsaicin into the skin of pigs actively sensitized with ascaris antigen caused a rapid light red-flare (vasodilation) reaction. Allergen and histamine, but not capsaicin, also produced plasma protein extravasation. In contrast to the absent flare, the protein extravasation response still occurred in capsaicin-treated pigs. The sensitivity to ascaris antigen was mediated by an IgE-like antibody. We conclude that a functional and morphological relationship exists between histamine-containing mast cells and capsaicin-sensitive sensory nerves in the pig skin. Mast cells and sensory nerves are also found in the airway mucosa and appear to be closely associated with the epithelium.

Animals↗
PubMed1991

Effects on immune responses in rats after neuromanipulation with capsaicin.

The effect of capsaicin treatment on the immune response, assessed as antibody formation in vivo and in vitro, was studied in ovalbumin (OA)-immunized rates. Rats were treated with capsaicin at 1-2 days of life or at adult age, before or after immunization. The levels of IgA, IgE and IgG antibodies as well as immunoglobulins were measured in serum and supernatants from cultured lymph node cells, spleen cells and peripheral blood lymphocytes. Capsaicin treatment affected the antibody levels depending on the timing of capsaicin treatment in relation to immunization. Different effects of capsaicin treatment were also observed on the different immunoglobulin isotypes. One of the most striking effects by capsaicin treatment was the reduction of IgA and IgG synthesis in cultured lymphoid cells from aerosol immunized animals treated with capsaicin after immunization. In contrast, in vivo the level of total serum IgA was increased in similarly treated animals. In this study we show that capsaicin treatment, which is known to decrease the levels of neuropeptides of sensory origin, has a time-dependent effect on both antibody levels in vivo as well as the formation of immunoglobulin in vitro. Although the mechanisms responsible for this are not obvious, we conclude a link between depletion of neuropeptides in sensory nerves and the antibody synthesis.

Animals↗
PubMed1991

Local immune response and bronchial reactivity in rats after capsaicin treatment.

The interaction between the nervous system, immune system and bronchial reactivity was studied in rats by using the neurotoxin capsaicin. Rats were treated with capsaicin at 1-2 days of age or at adult age, before or after sensitization by subcutaneous injections with ovalbumin (OA). The levels of the neuropeptides neurokinin A and calcitonin gene-related peptide were decreased in the lung after capsaicin treatment, as determined with radioimmunoassay, whereas the levels of neuropeptide Y were unaffected. The levels of IgA, IgE and IgG in bronchial lavage were also affected by capsaicin treatment; however, the results were heterogeneous. Capsaicin treatment after sensitization reduced the bronchial reactivity to challenge with OA aerosol and serotonin iv. The results demonstrated that reduction of neuropeptide levels with capsaicin affected both bronchial reactivity and the levels of antibodies in bronchial lavage fluid. However, no correlation between these two parameters was seen, demonstrating the complexity of the system.

Animals↗
PubMed1991

Effect of nedocromil sodium on allergen-, PAF-, histamine- and bradykinin-induced airways vasodilatation and pulmonary obstruction in the pig.

1. The influence of nedocromil sodium on the nasal and bronchial effects induced by allergen, platelet-activating factor (PAF), capsaicin, histamine and bradykinin aerosol challenge in ascaris-sensitized and pentobarbitone-anaesthetized pigs was studied. Blood flow changes in the bronchial and nasal circulation were measured with ultrasonic flow probes around the supplying arteries, and vascular resistance was calculated. Changes in pulmonary resistance (Rpulm), dynamic compliance (Cdyn), mean arterial pressure (MAP) and heart rate (HR) were also determined. 2. Allergen and PAF aerosol challenge in the lung produced similar effects consisting of both bronchial and nasal vasodilatation, bronchoconstriction (increase in Rpulm and decrease in Cdyn) and increases in MAP and HR. Local pretreatment with nedocromil sodium (80 mg, aerosol) reduced the peak and duration of both the bronchial vasodilatation and increase in Rpulm, while only the duration of the change in Cdyn was significantly decreased. Nedocromil sodium did not alter the increases in MAP and HR. The nasal vasodilatation evoked by PAF, but not allergen, challenge in the lung was reduced by nedocromil sodium. 3. Allergen challenge in the nose induced vasodilatation of long duration which was reduced by local nedocromil sodium pretreatment (50 micrograms kg-1, intra-arterially). 4. The vasodilator response to histamine aerosol was attenuated in the nasal, but not the bronchial circulation by local nedocromil sodium pretreatment. Histamine-induced bronchoconstriction was not altered by nedocromil sodium. 5. Bradykinin aerosol-induced vasodilatation in the nasal and bronchial circulation was markedly and equally reduced by local nedocromil sodium and systemic capsaicin (50 mg kg-1, s.c. 2 days before) pretreatment. 6. In conclusion, nedocromil sodium blocks some local vascular and bronchial effects, but not increases in MAP and HR, induced by allergen and PAF aerosol in the pig. Bradykinin-induced vasodilatation in the airways, which seems to be largely dependent on capsaicin-sensitive sensory nerves, is markedly inhibited by nedocromil sodium pretreatment, whereas capsaicin-induced vasodilatation is not affected by nedocromil sodium. It may be suggested that nedocromil sodium acts by inhibiting some common process involved in the release of mediators from inflammatory cells (when stimulated by allergen and PAF) and sensory nerves (when stimulated by bradykinin and histamine, but not capsaicin).

Allergens↗
PubMed1991

The possible role of prostaglandin D2 in the long-lasting airways vasodilatation induced by allergen in the sensitized pig.

Allergen-induced nasal and bronchial vasodilatation and bronchoconstriction were studied in ascaris-sensitized pigs with and without pretreatment with diclofenac sodium, to evaluate the contribution of prostanoids in these responses. The bronchoconstriction induced by allergen aerosol challenge was enhanced by diclofenac, whereas the duration of the bronchial vasodilatation was reduced from 80 to 30 min, without changing the maximal effect. However, both the maximal effect and the duration of the nasal vasodilatation were reduced upon nasal allergen challenge by 60% (P less than 0.01) and from 72 to 16 min (P less than 0.05), respectively. Bronchial challenge with the allergen also induced nasal vasodilatation of long duration and this response was highly sensitive to diclofenac pretreatment. I.v. injections of prostaglandins (PG) E1, E2, I2 and D2 revealed that only PGD2 induced vasodilatation of long duration in the airways without major effects on the systemic arterial blood pressure. Nebulization of PGD2 (0.7-1.4 mumol) into the pig airways also induced marked vasodilatation of long duration (greater than or equal to 40 min), especially in the nasal circulation. The vasodilatory responses to PGD2 were not changed by systemic pretreatment with capsaicin or diclofenac. Challenge in the airways with platelet-activating factor (PAF) produced bronchial and vascular responses similar to those seen with the allergen and the vasodilatory responses to PAF were partly sensitive to diclofenac. We propose that a long-lasting component of the allergen-induced vasodilatation in the pig airways, especially in the nasal mucosa, may be caused by the release of PGD2, acting independently of sensory nerves. Allergen and PAF aerosol challenge in the lung may also induce the release of a vasodilatory prostaglandin, possibly PGD2 into the systemic circulation, thereby inducing nasal vasodilatation.

Allergens↗
PubMed1991

Differential bronchial and pulmonary vascular responses to vagal stimulation in the pig.

The pulmonary and bronchial vascular responses and changes in bronchial tone upon vagal stimulation (240 impulses at 2 Hz or 10 Hz) were studied in anaesthetized pigs paralyzed with pancuronium. The acetylcholine-evoked vasodilatation in the tracheobronchial circulation had the same magnitude when using pancuronium or succinylcholine as skeletal muscle relaxants. Atropine-sensitive bradycardia, hypotension and bronchoconstriction were observed upon vagal stimulation. A vasoconstrictor response in the pulmonary vascular bed and clear-cut vasodilatation in the bronchial circulation supplied by the bronchial artery also occurred upon vagal stimulation. The vagally-evoked increase in pulmonary vascular resistance was markedly reduced after atropine while the bronchial vasodilatation was unchanged. This suggests that the vagally-induced increase in bronchial blood flow was not secondary to changes in the pulmonary circulation. Furthermore, the pulmonary vasoconstrictor response caused by vagal stimulation under control conditions is probably explained by reflex sympathetic activation due to the fall in systemic blood pressure. These data indicate selective vagal non-cholinergic influence of blood flow in the bronchial vascular bed compared to the pulmonary circulation.

Acetylcholine↗
PubMed1991

Sensory neuropeptide involvement in animal models of airway irritation and of allergen-evoked asthma.

C-fiber afferents in the airways are in close contact with mast cells and are activated both upon allergic reactions and by inhalation of irritants such as capsaicin and cigarette smoke. This evokes both protective reflexes such as cough as well as local release of tachykinins and calcitonin gene-related peptide (CGRP) with subsequent actions on blood vessels (vasodilatation and plasma protein extravasation) and bronchial smooth muscle (bronchoconstriction). After capsaicin pretreatment when peptides have been depleted from the sensory nerves, there is a marked reduction of the vasodilatatory response upon allergen challenge and the protein extravasation evoked by cigarette smoke. Conversely, chronic cigarette smoke exposure is accompanied by increased coughing to capsaicin challenge. Furthermore, aerosol immunization and chronic smoke exposure are both associated with elevated tissue levels of CGRP, suggesting upregulation of C-fiber function and peptide synthesis, which may contribute to airway hyperreactivity.

Aerosols↗
PubMed1991

Airways vasodilatation in the immediate allergic reaction. Involvement of inflammatory mediators and sensory nerves.

1. Systemic capsaicin treatment of the pig depletes the content of sensory neuropeptides (CGRP and tachykinins) in the airways mucosa and skin, without affecting sympathetic and parasympathetic nerves containing NPY and VIP, or the presence and appearance of inflammatory cells including mast cells. Acute capsaicin exposure caused release of sensory neuropeptides and catecholamines, and marked vasodilation in the airways and skin, without signs of plasma protein extravasation or bronchoconstriction. Capsaicin pretreatment effectively desensitizes against local challenges with capsaicin in the airways and skin, as revealed by the absence of vasodilatory responses 2 days later. 2. Cigarette smoke exposure induces marked vasodilatation, lasting for about 5 min in both the upper and lower airways, which seems not to be primarily caused by particulate matter or nicotine in the smoke. Except for a minor capsaicin-sensitive component in the nasal circulation, these responses probably do not involve neural activation, mast cell degranulation or prostaglandin formation. Rather, it is concluded that vapour phase components act on the vessels via unknown mechanisms. 3. Sensitization of pigs with s.c. injections of ascaris antigen was successful, resulting in typical wheal and flare reactions in the skin and bronchoconstriction after local challenge with antigen. The reactivity to ascaris is probably mediated by antibodies of the IgE isotype. 4. Histamine-containing mast cells and sensory neuropeptide-containing nerve fibers show close morphological association around blood vessels in the pig skin. Both alcian blue-positive mast cells and capsaicin-sensitive sensory nerves are present close to the pig airways epithelium. Sensory neuropeptide-containing nerves are also abundant around airways mucosal blood vessels, whereas the bronchial smooth muscle is sparsely innervated. 5. Allergen and histamine injections in the skin caused similar responses consisting of flare and protein extravasation. Allergen challenge in the airways induces marked vasodilatation lasting for 60-90 min in the pig bronchial and nasal circulations. Histamine seems to be important in the early phase (0-20 min) of these responses in the airways, while cyclooxygenase products (possibly PGD2) may be responsible for the longlasting component. A cyclo-oxygenase product is presumably also released from the lung into the circulation after bronchial allergen challenge and thereby induces a delayed, long-lasting nasal vasodilatation. Histamine may be the main bronchoconstrictor agent released in the immediate allergic reaction of the pig. 6. The flare, but not the protein extravasation reaction, to allergen and histamine injections in the skin, was inhibited by capsaicin pretreatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Endothelin-1 increases airway mucosa blood flow in the pig.

The vascular effects of bolus intravenous injections (4.5, 45 and 450 pmol.kg-1) of porcine endothelin-1 on the bronchial and nasal circulations were investigated in ten anesthetized pigs. Endothelin-1 produced a dose-dependent and long-lasting increase in bronchial blood flow with a concomitant rise in systemic arterial pressure suggesting vasodilatation. The highest doses of endothelin-1 also caused a slight decrease in the nasal vascular resistance. Furthermore, the vascular responses to endothelin-1 were not modified in systemically capsaicin pretreated animals or after pretreatment with a cyclocoxygenase inhibitor, diclofenac. Our results suggest that endothelin-1 has a potent and regional vasodiator effect of the bronchial circulation.

Animals↗