Bronchoprotective and bronchodilatory effects of deep inspiration in rabbits subjected to bronchial challenge

2001 ◽  
Vol 91 (6) ◽  
pp. 2511-2516 ◽  
Author(s):  
S. J. Gunst ◽  
X. Shen ◽  
R. Ramchandani ◽  
R. S. Tepper
Keyword(s):  
Human Subjects ◽  
Inhibitory Effect ◽  
Airway Responsiveness ◽  
Deep Inspiration ◽  
Contractile Apparatus ◽  
Airway Reactivity ◽  
Airway Response ◽  
Normal Human ◽  
Airway Responses

The effect of deep inspiration (DI) on airway responsiveness differs in asthmatic and normal human subjects. The mechanism for the effects of DI on airway responsiveness in vivo has not been identified. To elucidate potential mechanisms, we compared the effects of DI imposed before or during induced bronchoconstriction on the airway response to methacholine (MCh) in rabbits. The changes in airway resistance in response to intravenous MCh were continuously monitored. DI depressed the maximum response to MCh when imposed before or during the MCh challenge; however, the inhibitory effect of DI was greater when imposed during bronchoconstriction. Because immature rabbits have greater airway reactivity than mature rabbits, we compared the effects of DI on their airway responses. No differences were observed. Our results suggest that the mechanisms by which DI inhibits airway responsiveness do not depend on prior activation of airway smooth muscle (ASM). These results are consistent with the possibility that reorganization of the contractile apparatus caused by stretch of ASM during DI contributes to depression of the airway response.

ADRENERGIC CONTROL MECHANISM FOR ACTH SECRETION IN MAN

1973 ◽  
Vol 74 (2) ◽  
pp. 263-270 ◽  
Author(s):  
Yoshikatsu Nakai ◽  
Hiroo Imura ◽  
Teruya Yoshimi ◽  
Shigeru Matsukura
Keyword(s):  
Intravenous Infusion ◽  
Human Subjects ◽  
Blocking Agent ◽  
Inhibitory Effect ◽  
Plasma Acth ◽  
Acth Secretion ◽  
Glucose Levels ◽  
Alpha Receptors ◽  
Normal Human ◽  
Adrenergic Blocking

ABSTRACT In order to determine if an adrenergic mechanism is involved in the secretion of corticotrophin (ACTH), the effect of adrenergic-blocking or -stimulating agent on plasma ACTH, cortisol and glucose levels was studied in normal human subjects. The intravenous infusion of methoxamine, an alpha adrenergic-stimulating agent, caused a rise in plasma ACTH and cortisol. This increase in plasma ACTH and cortisol was significantly inhibited by the simultaneous administration of phentolamine, an alpha adrenergic-blocking agent, in combination with methoxamine. The intravenous infusion of propranolol, a beta adrenergic-blocking agent, caused no significant change in plasma ACTH and cortisol, although it enhanced the plasma ACTH response to insulin-induced hypoglycaemia. On the other hand, alpha adrenergicblockade by intravenous infusion of phentolamine significantly suppressed the plasma ACTH response to insulin-induced hypoglycaemia. These studies suggest a stimulatory effect of alpha receptors and a possible inhibitory effect of beta receptors on ACTH secretion in man.

Development and maintenance of force and stiffness in airway smooth muscle

2015 ◽  
Vol 93 (3) ◽  
pp. 163-169 ◽  
Author(s):  
Bo Lan ◽  
Brandon A. Norris ◽  
Jeffrey C.-Y. Liu ◽  
Peter D. Paré ◽  
Chun Y. Seow ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Solid State ◽  
Airway Smooth Muscle ◽  
Deep Inspiration ◽  
Contractile Apparatus ◽  
Tidal Breathing ◽  
Actomyosin Interaction ◽  
Filament Network

Airway smooth muscle (ASM) plays a central role in the excessive narrowing of the airway that characterizes the primary functional impairment in asthma. This phenomenon is known as airway hyper-responsiveness (AHR). Emerging evidence suggests that the development and maintenance of ASM force involves dynamic reorganization of the subcellular filament network in both the cytoskeleton and the contractile apparatus. In this review, evidence is presented to support the view that regulation of ASM contraction extends beyond the classical actomyosin interaction and involves processes within the cytoskeleton and at the interfaces between the cytoskeleton, the contractile apparatus, and the extracellular matrix. These processes are initiated when the muscle is activated, and collectively they cause the cytoskeleton and the contractile apparatus to undergo structural transformation, resulting in a more connected and solid state that allows force generated by the contractile apparatus to be transmitted to the extracellular domain. Solidification of the cytoskeleton also serves to stiffen the muscle and hence the airway. Oscillatory strain from tidal breathing and deep inspiration is believed to be the counter balance that prevents hypercontraction and stiffening of ASM in vivo. Dysregulation of this balance could lead to AHR seen in asthma.

scholarly journals Increased Excretion of C4-Carnitine Species after a Therapeutic Acetylsalicylic Acid Dose: Evidence for an Inhibitory Effect on Short-Chain Fatty Acid Metabolism

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Catharina M. C. Mels ◽  
Peet Jansen van Rensburg ◽  
Francois H. van der Westhuizen ◽  
Pieter J. Pretorius ◽  
Elardus Erasmus
Keyword(s):  
Fatty Acid ◽  
Acetylsalicylic Acid ◽  
Fatty Acid Metabolism ◽  
Short Chain Fatty Acid ◽  
Acid Metabolism ◽  
Human Subjects ◽  
Inhibitory Effect ◽  
Chain Fatty Acid ◽  
Short Chain

Acetylsalicylic acid and/or its metabolites are implicated to have various effects on metabolism and, especially, on mitochondrial function. These effects include both inhibitory and stimulatory effects. We investigated the effect of both combined and separate oral acetylsalicylic acid and acetaminophen administration at therapeutic doses on the urinary metabolite profile of human subjects. In this paper, we provided in vivo evidence, in human subjects, of a statistically significant increase in isobutyrylcarnitine after the administration of a therapeutic dose of acetylsalicylic acid. We, therefore, propose an inhibitory effect of acetylsalicylic acid on the short-chain fatty acid metabolism, possibly at the level of isobutyryl-CoA dehydrogenase.

Airway responses to inhaled histamine in asymptomatic smokers and nonsmokers

1977 ◽  
Vol 42 (4) ◽  
pp. 508-513 ◽  
Author(s):  
N. E. Brown ◽  
E. R. McFadden ◽  
R. H. Ingram
Keyword(s):  
Vital Capacity ◽  
Total Lung Capacity ◽  
Aerosol Deposition ◽  
Flow Volume ◽  
Maximal Flow ◽  
Airway Reactivity ◽  
Lung Capacity ◽  
Large Airway ◽  
Airway Response ◽  
Airway Responses

Bronchia reactivity to inhaled histamine was assessed in asymptomatic cigarette smokers and in nonsmoking atopic and nonatopic subjects. The only prechallenge between-group difference was the ratio of maximal flow on 80% helium-20% oxygen (Vmax HeO2) to maximal flow on air (Vmax air) from partial expiratory flow volume curves at 25% vital capacity (25% VC PEFV): Mean +/- SEM for smokers 1.18 /+- 0.06, atopics 1.45 +/- 0.08, nonatopics 1.51 +/- 0.03. This suggests that prior to inhalation to total lung capacity, the predominant site of resistance at flow limitation was in smaller airways of the smokers and in larger airways of both groups of nonsmokers. Following inhalation of histamine, smokers and nonatopics had similar changes in lung volumes and Vmax air which were less than in atopics. The Vmax HeO2/Vmax air ratios at 25% VC PEFV increased in smokers and decreased in nonsmokers: smokers 1.48 +/- 0.08, atopics 1.22 +/- 0.10, nontopics 1.16 +/- 0.06. This suggests a predominant large airway response in smokers and a prominent small airway response in nonsmokers. These responses may reflect differences in the predominant site of aerosol deposition rather than in airway reactivity.

Airway responses to inhaled ouabain and histamine in conscious guinea pigs

1986 ◽  
Vol 60 (6) ◽  
pp. 2089-2093 ◽  
Author(s):  
K. P. Agrawal ◽  
R. E. Hyatt
Keyword(s):  
Guinea Pigs ◽  
Airway Responsiveness ◽  
Maximal Response ◽  
Response Curves ◽  
Inhibiting Effect ◽  
Homeostatic Function ◽  
Positive Correlations ◽  
Airway Responses ◽  
Airway Conductance

Tracheal Na+-K+-ATPase activity is positively correlated with in vivo airway responsiveness to histamine. We wondered whether this were a chance association or whether it was directly related to the mechanism of hyperreactivity. Therefore, we obtained dose-response curves to aerosols of histamine and ouabain in guinea pigs to determine whether an in vivo relationship existed between the excitatory effects of histamine and the enzyme-inhibiting effect of ouabain. Airway responsiveness to ouabain was measured as the ouabain concentration producing a 30% decrease in specific airway conductance (ED30) or that producing a half-maximal response (ED50). Responsiveness to histamine was measured either as ED30 or as ED50. Significant positive correlations were noted between the log ED50 of ouabain and log histamine ED30 or ED50 (r = 0.81 and 0.83, respectively; P less than 0.001), and between log ouabain ED30 and log histamine ED30 and ED50 (r = 0.76 and 0.77, respectively; P less than 0.002). Pretreatment with ouabain increased airway responsiveness to histamine (P less than 0.05). We suggest that in hyperreactive airways Na+-K+-ATPase serves a homeostatic function of preventing Na+ and Ca2+ loading of the cell and that it is not directly responsible for the hyperreactivity.

Airways of a hyperresponsive rat strain show decreased relaxant responses to sodium nitroprusside

1995 ◽  
Vol 269 (1) ◽  
pp. L85-L91 ◽  
Author(s):  
Y. Jia ◽  
L. Xu ◽  
S. Heisler ◽  
J. G. Martin
Keyword(s):  
Sodium Nitroprusside ◽  
Inhibitory Effect ◽  
Airway Responsiveness ◽  
No Donor ◽  
Relaxant Effect ◽  
Inhibition Concentration ◽  
Relaxant Response ◽  
Rat Strain ◽  
Guanylyl Cyclase Activity

The aim of the current studies was to investigate the possibility that a decreased relaxant response to nitric oxide (NO) might contribute to strain-related differences in airway responsiveness in the rat. Isolated tracheal rings from hyperresponsive. Fisher rats were confirmed to be more responsive to carbachol [mean effective concentration (EC50) = 2.45 x 10(-7) M] than those from Lewis (EC50 = 3.60 x 10(-7) M, P < 0.03) and ACI (EC50 = 3.85 x 10(-7) M, P < 0.01) rats. Sodium nitroprusside (SNP), a NO donor, caused relaxation of the carbachol (10(-6) M) contracted tracheal rings, but the half-maximal inhibition concentration (IC50) SNP in Fisher rats (5.60 x 10(-6) M) was significantly higher than in Lewis (1.34 x 10(-6) M, P < 0.001) and ACI rats (1.13 x 10(-6) M, P < 0.0005). The inhibitory effect of SNP on airway responsiveness to inhaled methacholine (MCh) in vivo was also less pronounced for Fisher than Lewis rats. SNP induced an accumulation of guanosine 3',5'-cyclic monophosphate (cGMP) in cultured tracheal smooth muscle cells (TSM). Fisher TSM produced less cGMP on exposure to SNP compared with TSM from ACI (P < 0.01) and Lewis (P < 0.0001) rats. A decreased guanylyl cyclase activity may account for the impaired relaxant effect of SNP in Fisher rats.

Platelet catecholamines and platelet function in normal human subjects

1987 ◽  
Vol 73 (1) ◽  
pp. 99-103 ◽  
Author(s):  
A. P. Wilson ◽  
C. C. T. Smith ◽  
B. N. C. Prichard ◽  
D. J. Betteridge
Keyword(s):  
Platelet Function ◽  
High Performance ◽  
Human Subjects ◽  
Normal Subjects ◽  
Noradrenaline Content ◽  
Collagen Concentration ◽  
Normal Human ◽  
Wall Interaction ◽  
Local Release

1. We have used high-performance liquid chromatography with electrochemical detection to measure plasma and platelet catecholamines in 24 normal subjects. 2. In the same subjects platelet function was assessed by measuring platelet aggregation in response to adenosine 5′-pyrophosphate, thrombin, adrenaline and collagen. Platelet sensitivity to prostacyclin was also examined. 3. Platelet noradrenaline showed a positive correlation with extent of aggregation induced by ‘low-dose’ collagen (1 μg/ml). No correlation was seen at the higher collagen concentration. 4. Platelet noradrenaline content also correlated with sensitivity of platelets to prostacyclin. High platelet noradrenaline concentrations appeared to result in decreased sensitivity to prostacyclin. 5. No other correlations were observed. 6. These data suggest that platelet noradrenaline rather than plasma levels may be involved in modifying platelet function in vivo. Local release of platelet catecholamines may affect the platelet/vessel wall interaction, the primary physiological step in platelet activation.

Effect of 1,1-dimethylphenyl 1,4-piperazinium on mouse tracheal smooth muscle responsiveness

2005 ◽  
Vol 288 (6) ◽  
pp. L1139-L1145 ◽  
Author(s):  
G. Dorion ◽  
E. Israël-Assayag ◽  
M. J. Beaulieu ◽  
Y. Cormier
Keyword(s):  
Smooth Muscle ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Bronchial Hyperresponsiveness ◽  
Smooth Muscles ◽  
Inhibitory Effect ◽  
Tracheal Smooth Muscle ◽  
In Vivo Model ◽  
Airway Response

Bronchial hyperresponsiveness is one of the main features of asthma. A nicotinic receptor agonist, 1,1-dimethylphenyl 1,4-piperazinium (DMPP), has been shown to have an inhibitory effect on airway response to methacholine in an in vivo model of asthma. The aims of this study were to 1) verify whether nicotinic acetylcholine receptors (nAChR) were present on mouse tracheal smooth muscle, 2) verify whether bronchoprotection observed in mice was due to a direct effect on airway smooth muscle, and 3) compare the effects of nicotinic agonists to that of salbutamol. α3-, α4-, and α7-nAChR subunits were detected by immunofluorescence on tracheal tissues from normal BALB/c mice. The effect of DMPP on tracheal responsiveness was verified by an isometric method. Tracheas were isolated from normal mice, placed in organ baths, and contracted with a single dose of methacholine. Cumulative doses of DMPP or salbutamol were added to the baths. Results show that mouse tracheal smooth muscle is positive for α4- and α7-nAChR subunits and that the epithelium is positive for α3-, α4-, and α7-subunits. DMPP induced a greater dose-dependent relaxation of tracheal smooth muscles precontracted with methacholine than with salbutamol. These results suggest that the smooth muscle-relaxing effect of DMPP could have some interest in the treatment of obstructive pulmonary diseases.

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