Selective effect of general anesthetics on reflex bronchoconstrictor responses in dogs

Holtzman, Michael J.; Hahn, Hans Henning; Sasaki, Ken; Skoogh, Bengt-Eric; Graf, P D; Fabbri, Leonardo; Nadel, Jay A.

doi:10.1152/jappl.1982.53.1.126

Cited by 26 publications

(12 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These pathways are disrupted in the excised tissue, and a number of studies have shown that the activity of neural pathways can be compromised by anesthesia. For example, it is well documented that narcotic analgesics including pentobarbital sodium can block cholinergic neurotransmission (12,31).…”

Section: Discussionmentioning

confidence: 99%

Receptors and pathways mediating the effects of prostaglandin E₂ on airway tone

Tilley

Hartney

Erikson

et al. 2003

American Journal of Physiology-Lung Cellular and Molecular Phys

124

View full text Add to dashboard Cite

(PGE2) has complex effects on airway tone, and the existence of four PGE2 [E-prostanoid (EP)] receptors, each with distinct signaling characteristics, has provided a possible explanation for the seemingly contradictory actions of this lipid mediator. To identify the receptors mediating the actions of PGE2 on bronchomotor tone, we examined its effects on the airways of wild-type and EP receptor-deficient mice. In conscious mice the administration of PGE2 increased airway responsiveness primarily through the EP1 receptor, although on certain genetic backgrounds a contribution of the EP3 receptor was detected. These effects of PGE2 were eliminated by pretreatment with either atropine or bupivacaine and were undetectable in anesthetized mice or in denervated tracheal rings, where only EP2-mediated relaxation of airway smooth muscle was observed. Together, our findings are consistent with a model in which PGE2 modulates airway tone by activating multiple receptors expressed on various cell populations and in which the relative contribution of these receptors might depend on the expression of modifier alleles. PGE2/EP1/EP3-induced airway constriction occurs indirectly through activation of neural pathways, whereas PGE2-induced bronchodilation results from direct activation of EP2 receptors on airway smooth muscle. This segregation of EP receptor function within the airway suggests that PGE2 analogs that selectively activate the EP2 receptor without activating the EP1/EP3 receptors might prove useful in the treatment of asthma. PGE2 receptor; bronchoconstriction; bronchodilation; knockout; nerves SHORTLY AFTER ITS DISCOVERY in the 1960s, prostaglandin E 2 (PGE 2 ) was observed to have potent relaxant effects on airway smooth muscle, making this endogenous lipid an attractive candidate drug for asthma (18,34). However, human studies with aerosolized PGE 2 have demonstrated inconsistent effects on airway tone, with most asthmatics showing a bronchodilator response but some developing profound bronchoconstriction requiring beta agonist rescue (6,19). Ex vivo studies from humans and animals have also shown that PGE 2 can both relax and constrict airway smooth muscle, a paradox explained when it was recognized that PGE 2 could act through more than one receptor (9,20,26).Four distinct cell surface receptors for PGE 2 [E-prostanoid (EP)] have been identified and cloned, each with unique signal transduction mechanisms as a result of coupling to different G proteins (23). Activation of one or a combination of receptors, each which may be differentially expressed on airway smooth muscle, epithelia, neurons, and immune effector cells, results in a specific physiological response. EP2 and EP4 receptors couple to G s , and activation of these receptors results in stimulation of adenylyl cyclase and increases in intracellular cAMP. Various EP3 isoforms, arising from the differential splicing of the EP3 gene, have been identified both in humans and in mice (1,24). Differences in the cytoplasmic domain of the EP3 receptor leads to th...

show abstract

Section: Discussionmentioning

confidence: 99%

Receptors and pathways mediating the effects of prostaglandin E₂ on airway tone

Tilley

Hartney

Erikson

et al. 2003

American Journal of Physiology-Lung Cellular and Molecular Phys

124

View full text Add to dashboard Cite

show abstract

“…It has been reported that general anesthesia suppresses airway responsiveness [22, 23, 24]. Although the airway responsiveness was measured under the same conditions with and without PACAP to avoid the effect of anesthesia, a study using unanesthetized animals is needed in the future.…”

Section: Discussionmentioning

confidence: 99%

PACAP Reverses Airway Hyperresponsiveness Induced by Ozone Exposure in Guinea Pigs

Aizawa

Shigyo

Matsumoto³

et al. 1999

Respiration

View full text Add to dashboard Cite

Background: We previously demonstrated that pituitary adenylate cyclase activating peptide (PACAP) inhibits airway smooth muscle contraction and plasma extravasation. Objective: We thus hypothesized that PACAP may regulate airway responsiveness through these effects and examined the effects of exogenously applied PACAP on the airway hyperresponsiveness induced by ozone exposure. Methods: Ozone exposure was carried out in awake, spontaneously breathing guinea pigs using 3 ppm for 2 h. Airway responsiveness to histamine was determined before and 30 and 90 min after the termination of ozone exposure for 2 h in anesthetized animals. Extravasation of Evans blue was measured before and 90 min after the termination of ozone exposure. Either PACAP (10^–6 mol/kg) or vehicle was administered intravenously 60 min after exposure. The airway responsiveness was expressed as the concentration of histamine required to produce a 200% increase in total pulmonary resistance (PC₂₀₀). Results: Ozone exposure caused a significant decrease in PC₂₀₀ (n = 5, p < 0.05) 30 min after ozone exposure which persisted 90 min thereafter, thus suggesting that ozone caused airway hyperresponsiveness. PACAP significantly suppressed the increase in airway hyperresponsiveness induced by ozone 90 min after exposure (n = 5, p < 0.05). In contrast, this peptide did not have any effect on plasma extravasation. Conclusion: We thus conclude that PACAP decreases ozone-induced airway responsiveness, and, therefore, intravenously administered PACAP may be useful in reversing airway hyperresponsiveness.

show abstract

“…The type and level of anesthesia are im portant factors influencing airway re sponses to histamine [26,27], Reflex bronchoconstriction mediated by the vagus nerve is an important component of the response to histamine in dogs, and can be attenuated by general anesthesia, espe cially barbiturates [27]. In rabbits, pento barbital abolishes resting vagal tone on the heart, but reflex vagal activity is pre served [28].…”

Section: Discussionmentioning

confidence: 99%

Variability of Pulmonary Responsiveness to Aerosolized Histamine in Normal Rabbits

Quan¹,

Witten

Stevenson

et al. 1986

Respiration

View full text Add to dashboard Cite

Considerable between-subject variability in pulmonary responsiveness to histamine has been reported in normal human subjects, dogs, guinea pigs, and rhesus monkeys, but rabbits have not been studied. We determined the between- and within-rabbit variability of pulmonary histamine responsiveness in 34 anesthetized and mechanically ventilated New Zealand White rabbits. In 30 rabbits, 5 breaths of aerosolized histamine were delivered in 9 increasing concentrations ranging from 0.01 to 100 mg/ ml. Eleven of 30 rabbits were rechallenged with histamine on 1–4 additional occasions over a 3-week period. In the remaining 4 rabbits, 9 doses of distilled H₂O were aerosolized to determine the degree of spontaneous variability in measurements of lung resistance (Rl) and dynamic lung compliance (C_dyn)· We defined an increase in Rl of greater than 50% of baseline (TD₅₀R_L and a decrease in C_dyn of greater than 25% of baseline (TD₂₅C_dyn) as being significant based on observations in these 4 rabbits. These limits exceeded the 99.9 percentile of spontaneous variability in R_l and Cd_yn· Pulmonary responsiveness to histamine varied widely, with a greater than 10,000-fold range in TD₅₀R_L and a 1,000-fold range in TD₂₅C_dyn between the most and least sensitive rabbits. The variability of this responsiveness was log-normally distributed. It was not correlated with age, sex, or baseline Rl and C_dyn· In contrast, within-rabbit responses to histamine challenge were quite reproducible. Five of 30 rabbits were killed at the conclusion of their histamine challenges for pathologic examination of their lungs. No evidence of airway inflammation was found. We conclude that pulmonary histamine responsiveness in normal rabbits is qualitatively similar to that previously observed in guinea pigs and mongrel dogs, and may be an important factor in assessing airway reactivity in rabbit models of asthma

show abstract

Selective effect of general anesthetics on reflex bronchoconstrictor responses in dogs

Cited by 26 publications

References 0 publications

Receptors and pathways mediating the effects of prostaglandin E₂ on airway tone

Receptors and pathways mediating the effects of prostaglandin E₂ on airway tone

PACAP Reverses Airway Hyperresponsiveness Induced by Ozone Exposure in Guinea Pigs

Variability of Pulmonary Responsiveness to Aerosolized Histamine in Normal Rabbits

Contact Info

Product

Resources

About

Selective effect of general anesthetics on reflex bronchoconstrictor responses in dogs

Cited by 26 publications

References 0 publications

Receptors and pathways mediating the effects of prostaglandin E2 on airway tone

Receptors and pathways mediating the effects of prostaglandin E2 on airway tone

PACAP Reverses Airway Hyperresponsiveness Induced by Ozone Exposure in Guinea Pigs

Variability of Pulmonary Responsiveness to Aerosolized Histamine in Normal Rabbits

Contact Info

Product

Resources

About

Receptors and pathways mediating the effects of prostaglandin E₂ on airway tone

Receptors and pathways mediating the effects of prostaglandin E₂ on airway tone