Inhaled anandamide reduces leukotriene D4-induced airway obstruction in guinea pigs

2007 ◽  
Vol 557 (1) ◽  
pp. 66-68 ◽  
Author(s):  
Peter W. Stengel ◽  
Sandra L. Cockerham ◽  
Steven A. Silbaugh
Keyword(s):  
Airway Obstruction ◽  
Guinea Pigs ◽  
Leukotriene D4

Elevating dietary salt exacerbates hyperpnea-induced airway obstruction in guinea pigs

2001 ◽  
Vol 91 (3) ◽  
pp. 1061-1066 ◽  
Author(s):  
Timothy D. Mickleborough ◽  
Robert W. Gotshall ◽  
Jann Rhodes ◽  
Alan Tucker ◽  
Loren Cordain
Keyword(s):  
Airway Obstruction ◽  
Guinea Pigs ◽  
Nordihydroguaiaretic Acid ◽  
Baseline Period ◽  
Dietary Salt ◽  
Salt Loading ◽  
Salt Diet ◽  
Treatment Groups ◽  
Salt Consumption ◽  
Exercise Induced

Previous studies have indicated that increased dietary salt consumption worsens postexercise pulmonary function in humans with exercise-induced asthma (EIA). It has been suggested that EIA and hyperpnea-induced airway obstruction (HIAO) in guinea pigs (an animal model of EIA) are mediated by similar mechanisms. Therefore, the purpose of this study was to determine whether altering dietary salt consumption also exacerbated HIAO in guinea pigs. Furthermore, the potential pathway of action of dietary salt was investigated by blocking leukotriene (LT) production during HIAO in guinea pigs. Thirty-two male Hartley strain guinea pigs were split into two groups. One group ( n = 16) of animals ingested a normal-salt diet (NSD) for 2 wk; the other group ( n = 16) ingested a high-salt diet (HSD) for 2 wk. Thereafter, animals were anesthetized, cannulated, tracheotomized, and mechanically ventilated during a baseline period and during two dry gas hyperpnea challenges. After the first challenge, the animals were administered either saline or nordihydroguaiaretic acid, a LT inhibitor. Bladder urine was analyzed for electrolyte concentrations and urinary LTE4. The HSD elicited higher airway inspiratory pressures (Ptr) than the NSD ( P < 0.001) postchallenge. However, after infusion of the LT inhibitor and a second hyperpnea challenge, HIAO was blocked in both diet groups ( P < 0.001). Nonetheless, the HSD group continued to demonstrate slightly higher Ptr than the NSD group ( P < 0.05). Urinary LTE4 excretion significantly increased in the HSD group compared with the NSD group within treatment groups. This study has demonstrated that dietary salt loading exacerbated the development of HIAO in guinea pigs and that LT release was involved in HIAO and may be moderated by changes in dietary salt loading.

A comparison of the effect of inhaled diuretics on airway reflexes in humans and guinea pigs

1992 ◽  
Vol 72 (2) ◽  
pp. 434-438 ◽  
Author(s):  
J. A. Karlsson ◽  
N. B. Choudry ◽  
C. Zackrisson ◽  
R. W. Fuller
Keyword(s):  
Citric Acid ◽  
Guinea Pig ◽  
Airway Obstruction ◽  
Guinea Pigs ◽  
Airway Resistance ◽  
Loop Diuretic ◽  
Airflow Obstruction ◽  
Respiratory Resistance ◽  
Airway Mucosa ◽  
Maximum Inhibition

The effects of nebulized diuretics on citric acid-induced cough and airway obstruction in guinea pigs and capsaicin-induced cough and increase in airway resistance in humans have been studied. Half-maximum inhibition of cough in the guinea pig was produced by 1.3 mM furosemide and 0.25 mM hydrochlorothiazide. Cough was inhibited by 78 +/- 9% by 3 mM furosemide (P less than 0.05) and 89 +/- 11% by 3 mM hydrochlorothiazide (P less than 0.01). At the same time, airway obstruction was inhibited by 50 +/- 9% (P less than 0.001) and 42 +/- 15% (P less than 0.05), respectively. Nebulized furosemide (3 mM) was without effect on the airway obstruction produced by inhaled histamine or acetylcholine in the guinea pigs. Intravenously administered furosemide (270 nmol/kg) did not affect citric acid-induced responses. In humans, aerosolized furosemide (9 mM) and hydrochlorothiazide (3.4 mM) reduced the percent increase in respiratory resistance from 22.1 +/- 3.7 and 15.6 +/- 3.4 to 10.5 +/- 4.9 and 9.4 +/- 3.3%, respectively (P less than 0.05), but were without effect on cough due to capsaicin. Thus both furosemide and hydrochlorothiazide inhibited airway obstruction in the guinea pig and reduced the capsaicin-induced increase in airway resistance in humans. However, whereas coughing was inhibited in the guinea pig, neither drug affected cough in humans. This difference in the action of the loop diuretic and thiazide, which interact differently with Na(+)-K(+)-Cl-transport within the airway mucosa, on the cough and airflow obstruction in guinea pig and humans supports the view that different sensory limbs are involved in these reflexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacology of L-660,711 (MK-571): a novel potent and selective leukotriene D4 receptor antagonist

1989 ◽  
Vol 67 (1) ◽  
pp. 17-28 ◽  
Author(s):  
T. R. Jones ◽  
R. Zamboni ◽  
M. Belley ◽  
E. Champion ◽  
L. Charette ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Receptor Antagonist ◽  
Guinea Pigs ◽  
Competitive Inhibitor ◽  
Dose Ratio ◽  
Leukotriene D4 ◽  
Small Component ◽  
Human Trachea ◽  
D4 Receptor ◽  
Orally Active

L-660,711 (3-(3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl) ((3-dimethyl amino-3-oxo propyl)thio)methyl)thio)propanoic acid is a potent and selective competitive inhibitor of [3H]leukotriene D4 binding in guinea pig (Ki value, 0.22 nM) and human (Ki value, 2.1 nM) lung membranes but is essentially inactive versus [3H]leukotriene C4 binding (IC50 value in guinea pig lung, 23 μM). Functionally it competitively antagonized contractions of guinea pig trachea and ileum induced by leukotriene (LT) D4 (respective pA2 values, 9.4 and 10.5) and LTE4 (respective pA2 values, 9.1 and 10.4) and contractions of human trachea induced by LTD4 (pA2 value, 8.5). L-660,711 (5.8 × 10−8 M) antagonized contractions of guinea pig trachea induced by LTC4 in the absence (dose ratio = 28) but not in the presence of 45 mM L-serine borate (dose ratio <2). L-660,711 (1.9 × 10−5 M) did not block contractions of guinea pig trachea induced by histamine, acetylcholine, 5-hydroxytryptamine, PGF2α, U-44069, or PGD2. In the presence of atropine, mepyramine, and indomethacin, L-660,711 (1.9 × 10−5 M) inhibited a small component of the response to antigen on guinea pig trachea but completely blocked anti-IgE-induced contractions of human trachea. L-660,711 (i.v.) antagonized bronchoconstriction induced in anesthetized guinea pigs by i.v. LTC4, LTD4, and LTE4 but did not block bronchoconstriction to arachidonic acid, U-44069, 5-hydroxytryptamine, histamine, or acetylcholine. Intraduodenal L-660,711 antagonized LTD4 (0.2–12.8 μg/kg) -induced bronchoconstriction in guinea pigs, and p. o. L-660,711 blocked LTD4- and Ascaris-induced bronchoconstriction in conscious squirrel monkeys and ovalbumin-induced bronchoconstriction in conscious sensitized rats treated with methysergide (3 μg/kg). The pharmacological profile of L-660,711 indicates that it is a potent, selective, orally active leukotriene receptor antagonist which is well suited to determine the role played by LTD4 and LTE4 in asthma and other pathophysiologic conditions.

Differing mechanisms for leukotriene D4-induced bronchoconstriction in guinea pigs following intravenous and aerosol administration

1982 ◽  
Vol 24 (3) ◽  
pp. 419-432 ◽  
Author(s):  
R. Hamel ◽  
P. Masson ◽  
A.W. Ford-Hutchinson ◽  
T.R. Jones ◽  
G. Brunet ◽  
...  
Keyword(s):  
Guinea Pigs ◽  
Leukotriene D4

Leukotriene D4 potentiates histamine-induced bronchoconstriction in guinea-pigs

1984 ◽  
Vol 15 (3-4) ◽  
pp. 146-152 ◽  
Author(s):  
A. G. Stewart ◽  
D. C. Thompson ◽  
M. R. Fennessy
Keyword(s):  
Guinea Pigs ◽  
Leukotriene D4

scholarly journals DIETARY SALT CONSUMPTION AND LEUKOTRIENE-DEPENDENT HYPERPNEA-INDUCED AIRWAY OBSTRUCTION IN GUINEA PIGS

2001 ◽  
Vol 33 (5) ◽  
pp. S58
Author(s):  
T D. Mickleborough ◽  
R W. Gotshall ◽  
J Rhodes ◽  
A Tucker ◽  
L Cordain
Keyword(s):  
Airway Obstruction ◽  
Guinea Pigs ◽  
Dietary Salt ◽  
Salt Consumption
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