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At least 919 records · Page 51Linked to original sources
PubMed1975

Airway effects of slow reacting substance, prostaglandin F2alpha and histamine in the guinea-pig.

SRS, PGF2chi, and histamine were administered intravenously or as aerosols to artifically ventilated guinea-pigs in order to asses their capacity to affect tracheal insufflation pressure measured by means of Konzett-Rössler technique, Independently of route of administration all three compounds increased tracheal insufflation pressure, SRS being the most potent one. Bilateral cervical vagotomy did not alter the effect. Relative to histamine SRS and PGF2chi were considerably more active by aerosol administration than by intranvenous injection. The aerosols had little or no effect on systemic blood pressure. On intravenous injection, histamine decreased and SRS and PGF2chi increased arterial blood pressure in a dose-dependent fashion. The airway effects of histamine were correlated to those on blood pressure whereas with SRS and PGF2chi this was not seen when the blood pressure effects were marked. Preadministration of adrenaline or isoprenaline as aerosols antagonized the increase in insufflation pressure, but not the effects on blood pressure, produced by intravenously injected histamine or PGF2chi. It is concluded that SRS, PGF2chi and histamine on intravenous or aerosol adminstration increase tracheal insufflation pressure in the guinea-pig mainly by an action on airway tone. The data emphasize that SRS is a potent bronchoconstricting agent, possibly of pathophysiological significance in guinea-pig anaphylaxis.

Aerosols↗
PubMed1980

Pre- and postjunctional beta-adrenoceptor mediated effects on transmitter release and effector response in the isolated rat portal vein.

Pre- and postjunctional control mechanisms of the portal vein of spontaneously hypertensive rats (SHR) were characterized. Emphasis was placed on the influence of the presynaptic beta-adrenoceptor mediated mechanism for regulation of neuronal noradrenaline (NA) release (studied as tritium overflow) and its consequences for the contractile response under in vitro conditions. It was found that isoprenaline increased, whereas dl-propranolol decreased the release of neuronal NA during transmural nerve stimulation, while effector responses remained unaltered. d-Propranolol and the beta-1 selective adrenoceptor antagonist, metoprolol, did not affect these two variables. It is concluded that the presynaptic beta-adrenoceptors in the rat portal vein are mainly of the beta-2 type and mediate facilitation of neuronal transmitter release and that concomitant changes of the effector responses of this tissue are below the level of detection under the present experimental conditions.

Animals↗
PubMed1981

Evidence that substance P is a mediator of antidromic vasodilatation using somatostatin as a release inhibitor.

The effect of somatostatin on nerve-induced vasodilatation and the release of substance P (SP) was studied in the dental pulp of anesthetized cats. Changes in pulpal blood flow were determined by measuring the rate of disappearance of a local depot of radioactive tracer. The release of SP was studied indirectly by determining the residual amounts of substance P-like immunoreactivity (SPLI) in the pulps by radioimmunoassay. Electrical stimulation (3 min at 10 V, 15 Hz and 5 ms) of the distal end of the cut inferior alveolar nerve (IAN) increased pulpal blood flow. After pretreatment (10 min) with somatostatin (30 pmol/min) similar nerve stimulation was without effect on pulpal blood flow. Intra-arterial infusion of somatostatin (30 pmol/min) had no effect on pulpal blood flow and did not influence the vasodilator response to SP. Following IAN stimulation (3--45 min) and subsequent incubation (30 min, 37 degrees C) of the lower canine teeth, the SPLI levels in ipsilateral pulps were significantly lower (47.5% reduction) than those in contralateral, unstimulated controls. In cats pretreated with somatostatin (30 pmol/min for 10 min, i.a.) similar nerve stimulation (3 min) did not reduce the pulpal SPLI levels as compared to controls. The results show that nerve-induced vasodilatation and release of SPLI are inhibited by somatostatin. They are consistent with the hypothesis that vasodilatation in the cat dental pulp produced by stimulation of the IAN is mediated by substance P.

Alveolar Process↗
PubMed1993

Vascular leakage induced by histamine, bradykinin, serotonin and prostaglandin E2 in greyhounds.

Vascular leakage induced by intradermal injection of histamine, bradykinin and serotonin alone and co-injected with prostaglandin E2 was measured in Greyhounds using 125iodine-labelled human serum albumin (125I-HSA) as a marker in the blood. Histamine and bradykinin produced dose-dependent vascular leakage. At equimolar concentrations, histamine was more than twice as potent as bradykinin. Serotonin did not induce vascular leakage and was irritant. Prostaglandin E2 did not induce significant vascular leakage (maximum 5 microL) when injected alone, but when co-injected with histamine and bradykinin, the vascular leakage of both histamine and bradykinin was increased. This effect was more pronounced if lower concentrations of histamine and bradykinin were injected. The induced vascular leakage was greatest during the first five minutes of lesion development for histamine, during the second five minutes of lesion development for bradykinin, and the synergistic effect of prostaglandin E2 was maximal during the third five minute period of lesion development.

Animals↗
PubMed1983

Structure-activity relationships for some substance P-related peptides that cause wheal and flare reactions in human skin.

Substance P (6.25-25 p-mole) produced dose-dependent flare and wheal responses when injected intradermally into the volar surface of the human forearm. The maximum flare response was obtained within the first 3 min of injection and declined thereafter. The wheal response reached a maximum after 12 min following the injection. Only those peptides having one or more basic residues in the N-terminal region were effective in producing a flare reaction. Eledoisin-related peptide and SP1-9 were 17 and 7 times less active than substance P respectively, whilst [D-pro2, D-phe7, D-trp9]SP1-11 was twice as active. The N-terminal tetrapeptide, SP1-4 and eledoisin were inactive in the dose range tested. Wheal-producing activity was not dependent on the presence of basic residues and the rank order of relative potencies was: physalaemin (2.0): [D-pro2, D-phe7, D-trp9]SP1-11 (1.1): SP1-11 (1.0): SP4-11 (0.4): SP1-9 (0.15): eledoisin-related peptide (0.08): eledoisin (0.06). The N-terminal tetrapeptide failed to produce a wheal response in the dose range tested. Substance P was approximately equi-active with poly-L-arginine in the production of wheal and flare and both of these agents were about 10 times more potent than histamine. Adenosine triphosphate (25-400 n-mole) produced dose-dependent wheal and flare responses and was 10,000 times less potent than substance P. Pre-treatment of the subjects with the H1 histamine antagonist, chlorpheniramine, (20 mg I.V.) reduced the wheal and flare responses to substance P. Local anaesthetic injection into the skin reduced the spread of the flare response but did not affect the development of the wheal response. Pre-treatment of the skin with capsaicin reduced the flare but not the wheal response to intradermal injection of histamine. The results are discussed in relation to the mechanism of the 'axon reflex' vasodilatation in skin. This is thought to involve mast cells in addition to substance P-containing primary afferent neurones.

Adenosine Triphosphate↗
PubMed1990

Effects of qing-fei-tang on the airway inflammation and clearance.

Qing-Fei-Tang, a Chinese blended medicine, inhibited the release of slow reacting substance of anaphylaxis (SRS-A) from passively sensitized guinea pig lung after antigen challenge. Qing-Fei-Tang also suppressed the chemiluminescence of oxygen radicals when healthy human leukocytes were stimulated by opsonized zymosan. In rabbits, Qing-Fei-Tang increased the output volume and fatty acid contents in respiratory tract fluid. In the bronchitic rabbits, 6 weeks administration of Qing-Fei-Tang restored the decreased amount of saturated fatty acid in the sputa, and histological examinations revealed an amelioration of the inflammation of lung tissues. In pigeons, Qing-Fei-Tang facilitated tracheal mucociliary transport. Accordingly, Qing-Fei-Tang seems to exert effectiveness via its multiple mechanisms.

Animals↗
PubMed1985

Capsaicin effects on muscularis mucosa of opossum esophagus: substance P release from afferent nerves?

The effects of capsaicin on the function and structure of muscularis mucosa of opossum esophagus were studied. In this tissue there are numerous nerves containing a substance P-like immunoreactive substance (SPLS), and electrical field stimulation (EFS) leads to a phasic response that appears to be due to release of acetylcholine, followed by a tonic response at higher frequencies of stimulation that appears to be due to release of a SPLS. The acetylcholine released by EFS and exogenous muscarinic agonists inhibits release of this SPLS (8). In the present study capsaicin (5 X 10(-5) M) was shown to cause a tonic submaximal contraction in most cases. This was prevented by substance P tachyphylaxis and by pretreatment with the partial agonist [D-Pro2, D-Trp7,9]substance P, the antagonist [D-Arg1, D-Trp7, Leu11]substance P, and tetrodotoxin. This response to capsaicin could not be repeated even after 2 h. Capsaicin also abolished the tonic response to high-frequency EFS without affecting phasic responses and reduced markedly the enhanced tonic response after atropine had abolished the phasic response. This occurred with or without a preliminary contraction to capsaicin. This tonic response to high-frequency EFS recovered completely 1-2 h after washing out capsaicin. Then, a further administration of capsaicin had no direct effect but again abolished tonic responses to EFS. Capsaicin reduced responses to exogenous substance P or carbachol only partially. When tissues were fixed and studied after capsaicin had abolished tonic responses to EFS, specific damage to nerve varicosities or synaptic vesicles in nerve varicosities could not be demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed2006

Mechanistic studies of acid-evoked coughing in anesthetized guinea pigs.

Experiments carried out in conscious guinea pigs suggest that citric acid-evoked coughing is partly mediated by transient receptor potential vanilloid type 1 (TRPV1) receptor-dependent activation of tachykinin-containing, capsaicin-sensitive C fibers. In vitro electrophysiological analyses indicate, however, that acid also activates capsaicin-sensitive and -insensitive vagal afferent nerves by a TRPV1-independent mechanism, and studies in anesthetized guinea pigs show that coughing evoked by acid is mediated by activation of capsaicin-insensitive vagal afferent nerves. In the present study, we have characterized the mechanisms of citric acid-evoked coughing in anesthetized guinea pigs. Drugs were administered directly to the Krebs buffer perfusing the extrathoracic trachea. Citric acid was applied topically to the tracheal mucosa, directly into the tracheal perfusate in increasing concentrations and at 1-min intervals. Citric acid dose dependently evoked coughing in anesthetized guinea pigs. This was mimicked by hydrochloric acid but not by sodium citrate. The coughing evoked by acid was nearly or completely abolished by TTX or by cutting the recurrent laryngeal nerves. Perfusing the trachea with a low Cl- buffer potentiated the acid-induced cough reflex. In contrast, prior capsaicin desensitization, 10 microM capsazepine, Ca2+-free perfusate, 0.1 microM iberiotoxin, 1 microM atropine, 10 microM isoproterenol, 10 microM albuterol, 3 microM indomethacin, 0.1 microM HOE-140, a combination of neurokinin1 (NK1; CP-99994), NK2 (SR-48968), and NK3 (SB-223412) receptor antagonists (0.1 microM each), a combination of histamine H1 (3 microM pyrilamine) and cysLT1 (1 microM ICI-198615) receptor antagonists, superior laryngeal nerve transection, or epithelium removal did not inhibit citric acid-evoked coughing. These and other data indicate that citric acid-evoked coughing in anesthetized guinea pigs is mediated by direct activation of capsaicin-insensitive vagal afferent nerves, perhaps through sequential activation of acid-sensing ion channels and chloride channels.

Anesthesia↗
PubMed1994

Vasopressin-independent regulation of collecting duct water permeability.

Studies were conducted in microdissected rat terminal inner medullary collecting duct (IMCD) segments to determine whether agents that activate the phosphoinositide signaling pathway regulate osmotic water permeability independent of the action of vasopressin. Water was withheld from the rats for 24 h before the experiments, a procedure that yields a stably high osmotic water permeability in isolated perfused terminal IMCDs in the absence of vasopressin. In the present studies, the vasopressin-independent osmotic water permeability was sustained at approximately 300 microns/s for at least 90 min. We used the cholinergic agent carbachol (10-100 microM) to activate the phosphoinositide pathway. This agent has previously been reported to increase the hydrolysis of inositol phospholipids in IMCD cells without altering adenosine 3',5'-cyclic monophosphate production. In preliminary studies, we demonstrated (using fura 2) that carbachol transiently increases intracellular calcium and that this response was blocked by atropine, confirming that muscarinic receptors are coupled to activation of the phosphoinositide signaling pathway in these cells. In the absence of vasopressin, both carbachol (10 microM) and phorbol myristate acetate (1 nM) inhibited osmotic water permeability by 40-50% within 10 min. These effects were partially blocked by calphostin C, an inhibitor of protein kinase C. These results demonstrate that activation of phosphatidylinositol hydrolysis and/or activation of protein kinase C markedly inhibits osmotic water permeability in isolated perfused IMCD segments, even in the absence of prior stimulation by vasopressin.

Animals↗
PubMed1987

A formyl peptide contracts guinea pig lung: role of arachidonic acid metabolites.

We studied the role of cyclooxygenase and lipoxygenase products of arachidonic acid metabolism in mediating N-formyl-methionyl-leucyl-phenylalanine- (FMLP) induced contractions of guinea pig lung parenchymal strips. The cyclooxygenase inhibitors indomethacin (10(-5) M) and aspirin (3 X 10(-5) to 10(-4) M), the lipoxygenase inhibitor nordihydroguaiaretic acid (10(-5) to 3 X 10(-5) M), and the combined cyclooxygenase/lipoxygenase inhibitors 1-phenyl-3-pyrazolidinone (Phenidone) (3 X 10(-5) to 3 X 10(-4) M) and BW 755C (10(-5) to 10(-4) M) each caused a decrease in the maximum force induced by FMLP (Fmax) and an increase in the concentration of FMLP required to produce 50% of Fmax (EC50). The thromboxane synthesis inhibitor imidazole (3 X 10(-3) M) also decreased Fmax. The leukotriene D4 receptor antagonist FPL 55712 (5.7 X 10(-6) to 1.9 X 10(-5) M) increased the EC50 for FMLP, whereas desensitization of lung parenchymal strips to leukotriene B4 by pretreatment with this leukotriene (10(-7) M) had no effect on FMLP-induced contraction. After exposure to FMLP (10(-6) M), guinea pig lung produced (as determined by high-performance liquid chromatography and radioimmunoassay) leukotrienes C4 and B4, thromboxane A2 (as measured by its stable degradation product thromboxane B2), and prostaglandin F2 alpha. Lung strips not exposed to FMLP showed no evidence of leukotriene production. We conclude that thromboxane A2 and leukotriene C4 generated in response to FMLP mediate a substantial fraction of the force induced by this peptide in guinea pig lung parenchymal strips.

Acetophenones↗
PubMed1990

Role of leukotrienes during oleic acid-induced lung injury in pigs.

We hypothesized that leukotrienes might contribute to the pathophysiology of acute lung injury induced by oleic acid. Oleic acid (2-20 mg.kg-1.h-1), LY171883 [leukotriene (LT) D4/LTE4 receptor antagonist, 10 mg/kg + 1 mg.kg-1.h-1] + oleic acid (10 mg.kg-1. h-1), or triolein (20 mg.kg-1.h-1) were infused intravenously into anesthetized pigs. Treatment with the cyclooxygenase inhibitor was designed to possibly enhance LT release. Bronchoalveolar lavage fluid concentrations of LTB4, LTC4, LTD4, and LTE4 were measured by reverse-phase high-performance liquid chromatography and radioimmunoassay. Oleic acid caused dose-related hypoxemia and pulmonary hypertension and increased pulmonary vascular resistance, lung water, and alveolar-capillary membrane permeability. Bronchoalveolar lavage fluid levels of LTB4, LTC4, LTD4, and LTE4 showed no significant changes in oleic acid- or indomethacin + oleic acid-treated pigs, compared with triolein-treated controls. Indomethacin modestly attenuated the oleic acid-induced hypoxemia and the early increases (i.e., 0-0.5 h) in mean pulmonary arterial pressure and pulmonary vascular resistance. In contrast, LY171883 provided no protection against any oleic acid-induced cardiopulmonary effect (measured or calculated). We conclude that LTs are not likely to be important mediators of oleic acid-induced lung injury in the pig.

Acetophenones↗
PubMed1990

Effect of LY171883 on endotoxin-induced lung injury in pigs.

We evaluated the role of sulfidopeptide leukotrienes as mediators of endotoxin-induced respiratory failure in pigs. Escherichia coli endotoxin (055-B5) was infused intravenously into anesthetized 10- to 14-wk-old pigs at 5 micrograms/kg the 1st h followed by 2 micrograms.kg-1.h-1 for 3 h in the presence and absence of LY171883, a specific leukotriene D4 (LTD4)/LTE4 receptor antagonist. Endotoxin caused hemoconcentration, granulocytopenia, decreased cardiac index, systemic hypotension, pulmonary hypertension, increased pulmonary vascular resistance, bronchoconstriction, hypoxemia, increased permeability of the alveolar-capillary membrane, pulmonary edema, and increased plasma concentrations of thromboxane B2 (TxB2), prostaglandin F2 alpha (PGF2 alpha), and 6-keto-PGF1 alpha. LY171883 did not modify endotoxin-induced cardiopulmonary and hematologic abnormalities, except for a modest attenuation of pulmonary hypertension (at 1 h) and increased pulmonary vascular resistance (at 1-2 h). Ex vivo stimulation of whole blood with calcium ionophore caused large increases in plasma concentrations of TxB2, PGF2 alpha, and LTB4. These increases were not significantly modified in blood derived from pigs treated with LY171883, indicating no inhibition of cyclooxygenase or 5-lipoxygenase. We conclude that LTD4 and LTE4 are not important mediators of endotoxin-induced lung injury in anesthetized pigs, although they may contribute modestly to pulmonary vasoconstriction.

Acetophenones↗