Reversal of 5HT-induced bronchoconstriction by PGI2: distribution of central and peripheral actions

1980 ◽  
Vol 49 (3) ◽  
pp. 521-527 ◽  
Author(s):  
E. W. Spannhake ◽  
J. L. Levin ◽  
B. T. Mellion ◽  
C. A. Gruetter ◽  
A. L. Hyman ◽  
...  
Keyword(s):  
Lung Compliance ◽  
Pulmonary Mechanics ◽  
Similar Distribution ◽  
Mechanically Ventilated ◽  
Peripheral Airways ◽  
Bolus Intravenous Injection ◽  
Peripheral Areas ◽  
Dynamic Lung Compliance ◽  
Dose Dependent

In anesthetized, mechanically ventilated, and vagotomized cats, we studied the distribution of the bronchodilatory effects of prostaglandin I2 (PGI2) in central and peripheral airways. In the intact-chest cat, bolus intravenous injection of PGI2 in a range of doses from 3 to 100 micrograms produced dose-dependent reversal of 5-hydroxytryptamine- (5HT) induced bronchoconstriction. Bronchodilatory effects were manifested by a pronounced decrease in central airways flow resistance, as estimated by measurement of lung resistance and by an increase in dynamic lung compliance (Cdyn). A similar distribution and magnitude of airway effects were produced by intravenous administration of PGE1 in a range of doses from 0.3 to 10 micrograms. PGI2 significantly reversed the frequency dependence of compliance induced by infusion of 5HT. The PGI2 metabolite, 6-keto-PGF1 alpha, was without effect on pulmonary mechanics. Comparison of right- versus left-heart administration of PGI2 did not point to a significant role of the bronchial circulation in the airway effects of PGI2. Comparison of the effects of PGI2 and PGE1 on cat bronchial and parenchymal strips contracted by 5HT showed both prostaglandins to have predominant action on bronchial smooth muscle with PGI2 being 3-10 times less active than PGE1. These data suggest that PGI2 has central airway bronchodilator activity, similar to, but less potent than PGE1. In addition, they suggest that PGI2 has significant dilator activity in certain peripheral areas of the lung, as well.

Role of tachykinins in ozone-induced airway hyperresponsiveness to cigarette smoke in guinea pigs

1997 ◽  
Vol 83 (3) ◽  
pp. 958-965 ◽  
Author(s):  
Zhong-Xin Wu ◽  
Robert F. Morton ◽  
Lu-Yuan Lee
Keyword(s):  
Cigarette Smoke ◽  
Guinea Pigs ◽  
Airway Hyperresponsiveness ◽  
Lung Compliance ◽  
Smoke Inhalation ◽  
Before And After ◽  
Sham Exposure ◽  
Inhalation Challenge ◽  
Dynamic Lung Compliance

Wu, Zhong-Xin, Robert F. Morton, and Lu-Yuan Lee. Role of tachykinins in ozone-induced airway hyperresponsiveness to cigarette smoke in guinea pigs. J. Appl. Physiol. 83(3): 958–965, 1997.—Acute exposure to ozone (O3) induces airway hyperresponsiveness to various inhaled bronchoactive substances. Inhalation of cigarette smoke, a common inhaled irritant in humans, is known to evoke a transient bronchoconstrictive effect. To examine whether O3 increases airway responsiveness to cigarette smoke, effects of smoke inhalation challenge on total pulmonary resistance (Rl) and dynamic lung compliance (Cdyn) were compared before and after exposure to O3 (1.5 ppm, 1 h) in anesthetized guinea pigs. Before O3 exposure, inhalation of two breaths of cigarette smoke (7 ml) at a low concentration (33%) induced a mild and reproducible bronchoconstriction that slowly developed and reached its peak (ΔRl= 67 ± 19%, ΔCdyn = −29 ± 6%) after a delay of >1 min. After exposure to O3 the same cigarette smoke inhalation challenge evoked an intense bronchoconstriction that occurred more rapidly, reaching its peak (ΔRl = 620 ± 224%, ΔCdyn = −35 ± 7%) within 20 s, and was sustained for >2 min. By contrast, sham exposure to room air did not alter the bronchomotor response to cigarette smoke challenge. Pretreatment with CP-99994 and SR-48968, the selective antagonists of neurokinin type 1 and 2 receptors, respectively, completely blocked the enhanced responses of Rl and Cdyn to cigarette smoke challenge induced by O3. These results show that O3 exposure induces airway hyperresponsiveness to inhaled cigarette smoke and that the enhanced responses result primarily from the bronchoconstrictive effect of endogenous tachykinins.

Prolonged methacholine-induced bronchoconstriction in dogs

1979 ◽  
Vol 47 (2) ◽  
pp. 418-424 ◽  
Author(s):  
J. W. Ramsdell ◽  
P. F. Georghiou
Keyword(s):  
Lung Function ◽  
Gas Exchange ◽  
Lung Compliance ◽  
Cholinergic Stimulation ◽  
Partial Pressure Of Oxygen ◽  
Pulmonary Resistance ◽  
Mechanically Ventilated ◽  
Arterial Partial Pressure ◽  
Dynamic Lung Compliance ◽  
And Control

We studied the effect of prolonged airways obstruction induced by extended cholinergic stimulation in five anesthetized, mechanically ventilated dogs. A continuous intravenous metacholine infusion was utilized to maintain pulmonary resistance (RL) at 200--1500% preinfusion levels for 13--23 h. At maximum RL (18.86 +/- 7.74 vs. 2.09 +/- 0.18 (mean +/- SD) cmH2O/ (L/S) PREINfusion; P less than 0.01), dynamic lung compliance (Cdyn) fell from 67.5 +/- 14.6 to 32.7 +/- 11.6 ml/cmH2O (P less than 0.005) and arterial partial pressure of oxygen (PaO2) fell modestly from 95.8 +/- 6.1 Torr preinfusion to 83.2 +/- 12.7 Torr (P less than 0.05). Tachyphylaxis to methacholine developed, requiring increases in infusion rates to maintain elevated RL. Abnormalities in lung function resolved promptly upon termination of the infusion. Two similarly instrumented control animals ventilated for 19 and 25 h without metacholine infusion had no change in RL, Cdyn, or PaO2. Histological examination of the lungs revealed no differences between infused and control animals. In spite of marked increases in RL, prolonged cholinergic stimulation produced only mild changes in gas exchange and no sustained changes in lung function or structure.

Serial distribution of airway mechanical properties in dogs: effects of histamine

1994 ◽  
Vol 77 (2) ◽  
pp. 554-566 ◽  
Author(s):  
R. H. Habib ◽  
B. Suki ◽  
J. H. Bates ◽  
A. C. Jackson
Keyword(s):  
Mechanical Properties ◽  
Model Fit ◽  
Control Case ◽  
Frequency Range ◽  
Mechanically Ventilated ◽  
Peripheral Airways ◽  
Direct Measurements ◽  
Airway Opening ◽  
Bolus Intravenous Injection ◽  
Airway Walls

We measured respiratory input impedance (Zin; 8–2,048 Hz) in five dogs (anesthetized, tracheostomized, vagotomized, and mechanically ventilated) during 80 s of apnea after a bolus intravenous injection of saline or histamine (5.0 mg). In the control case, three antiresonances in Zin were found in four of the dogs, whereas in the remaining dog only two were found. The magnitude and frequency of these antiresonances were significantly altered after bronchoconstriction. To interpret Zin, a model incorporating detailed airway geometry, asymmetrical branching, and nonrigid airway walls was developed. The model fit both the saline and histamine Zin data well and predicted a serial distribution of bronchoconstriction consistent with known effects of histamine; i.e., the diameters of the most peripheral airways were reduced (26% of their control values), whereas tracheal diameters were not significantly affected. The model provided estimates of tracheal diameters that were well correlated (r = 0.92) with direct measurements. Control estimates of soft tissue viscosity (1.63 +/- 0.42 cmH2O.s) and Young's modulus (406 +/- 125 cmH2O) compared closely with values in the literature. These results indicate that bronchoconstriction induced by histamine results in significant changes in Zin over this frequency range and that by using this data analysis approach definitive physiological parameters relative to airway geometry and wall mechanical properties can be obtained from measurements made at the airway opening.

Pulmonary mechanics during the ventilatory response to hypoxemia in the newborn monkey

1983 ◽  
Vol 55 (3) ◽  
pp. 1008-1014 ◽  
Author(s):  
W. A. LaFramboise ◽  
R. D. Guthrie ◽  
T. A. Standaert ◽  
D. E. Woodrum
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Lung Compliance ◽  
Pulmonary Mechanics ◽  
Base Line ◽  
Respiratory Drive ◽  
Pulmonary Resistance ◽  
Residual Capacity ◽  
Dynamic Lung Compliance ◽  
Sustained Increase

Dynamic lung compliance (CL), inspiratory pulmonary resistance (RL), and functional residual capacity (FRC) were measured in 10 unanesthetized 48 h-old newborn monkeys and seven 21-day-old infant monkeys during acute exposures to an equivalent level of hypoxemia. End-expiratory airway occlusions were performed and the pressure developed by 200 ms (P0.2) was utilized as an index of central respiratory drive. P0.2 demonstrated a sustained increase throughout the period of hypoxemia on day 2 despite the fact that minute ventilation (VI) initially increased but then fell back to base-line levels. Dynamic lung compliance fell and FRC increased by 5 min of hypoxemia in the newborns. The 21-day-old monkeys exhibited a sustained increase in both VI and P0.2 throughout the hypoxic period with no change in CL and FRC. RL did not change at either postnatal age during hypoxemia. These data indicate that the neonatal monkey is subject to changes in pulmonary mechanics (decreased CL and increased FRC) during hypoxemia and that these changes are eliminated with maturation.

Role of endothelium-derived relaxing factor in active hyperemia of the canine diaphragm

1992 ◽  
Vol 72 (6) ◽  
pp. 2393-2401 ◽  
Author(s):  
S. N. Hussain ◽  
D. J. Stewart ◽  
J. P. Ludemann ◽  
S. Magder
Keyword(s):  
Vascular Resistance ◽  
Systemic Circulation ◽  
Mechanically Ventilated ◽  
Relaxing Factor ◽  
Arterial Blood ◽  
Left Diaphragm ◽  
Phrenic Artery ◽  
Endothelium Derived Relaxing Factor ◽  
Dose Dependent

To assess the effect of endothelium-derived relaxing factor (EDRF) on diaphragmatic vascular resistance at rest and during contractions, we studied an in situ isolated diaphragm preparation in anesthetized and mechanically ventilated dogs. The arterial supply of the left diaphragm (phrenic artery) was catheterized and perfused with arterial blood at a fixed flow rate. Drugs were infused through a side port of the arterial catheter at 1/100th of the phrenic arterial flow. The inferior phrenic vein was catheterized to complete the isolation from the systemic circulation. Three sets of experiments were performed. In set 1 (n = 3), we infused endothelium-dependent (acetylcholine, ACh) and endothelium-independent (sodium nitroprusside, SNP) dilators at increasing concentrations. ACh and SNP infusion elicited a dose-dependent decline in phrenic vascular resistance (Rphr) at concentrations greater than 10(-8) M and 0.50 micrograms/ml, respectively. In set 2 (n = 15), we infused an inhibitor of EDRF synthesis and release, L-argininosuccinic acid (ArgSA), at increasing concentrations (10(-4), 3 x 10(-4), and 6 x 10(-4) M). ArgSA produced a dose-dependent increase in Rphr. Infusion of another EDRF inhibitor (NG-nitro-L-arginine, LNA, 6 x 10(-4) M) elicited increase in Rphr similar to that induced by ArgSA. In set 3 (n = 25), we infused ArgSA or LNA (6 x 10(-4) M) simultaneously with ACh and SNP and during sustained (2-Hz) contractions of the diaphragm. Both ArgSA and LNA completely reversed ACh vasodilation, whereas SNP vasodilation was reversed by 26 and 11%, respectively. ArgSA or LNA infusion during contractions reversed vasodilation by 48 and 52%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of tachykinins in sulfur dioxide-induced bronchoconstriction in anesthetized guinea pigs

1996 ◽  
Vol 80 (6) ◽  
pp. 2044-2050 ◽  
Author(s):  
A. M. Hajj ◽  
N. K. Burki ◽  
L. Y. Lee
Keyword(s):  
Sulfur Dioxide ◽  
Guinea Pigs ◽  
Lung Compliance ◽  
Arterial Blood ◽  
Baseline Values ◽  
Nk2 Receptor ◽  
Dynamic Lung Compliance ◽  
Sensory Endings ◽  
Made In

To investigate the role of tachykinin release in mediating the bronchoconstrictive effect of sulfur dioxide (SO2) inhalation, measurements of dynamic lung compliance (Cdyn), total pulmonary resistance (RL), and arterial blood pressure (ABP) were made in anesthetized guinea pigs. Brief exposure (six tidal breaths) to SO2 at concentrations between 500 and 2,000 parts/million resulted in a concentration-dependent increase in RL, decrease in Cdyn, and systemic hypotension. For example, SO2 at 2,000 parts/million induced reversible and reproducible changes in RL, Cdyn, and ABP of 1,041 +/- 234, -60 +/- 6, and -25.8 +/- 4.3% of the baseline values, respectively. Pretreatment with two selective neurokinin- (NK) receptor (NK1 and NK2) antagonists, CP-99994 and SR-48968, resulted in almost complete inhibition of the increase in RL and of the decrease in Cdyn while preserving the decrease in ABP. Antagonism of the NK2 receptor alone resulted in inhibition of the majority of the SO2-induced bronchoconstriction, whereas that of the NK1 and muscarinic receptors did not have a significant effect. We conclude that the release of tachykinins from sensory endings plays a central role in SO2-induced bronchoconstriction in anesthetized guinea pigs, primarily via the activation of the NK2 receptor.

Role of nitric oxide and prostaglandins in the regulation of diaphragmatic arteriolar tone in the rat

1994 ◽  
Vol 77 (2) ◽  
pp. 590-596 ◽  
Author(s):  
J. Boczkowski ◽  
E. Vicaut ◽  
G. Danialou ◽  
M. Aubier
Keyword(s):  
Nitric Oxide ◽  
Prostaglandin Synthesis ◽  
Relative Importance ◽  
Mechanically Ventilated ◽  
Arteriolar Tone ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Arteriolar Diameter ◽  
Specific Inhibitors

We evaluated by intravital microscopy in rats the relative importance of nitric oxide (NO) and prostaglandins in 1) the maintenance of basal diaphragmatic arteriolar tone and 2) the response of diaphragmatic arterioles to the endothelium-dependent vasodilator acetylcholine (ACh). One hundred two mechanically ventilated rats were studied. Separate applications of N omega-nitro-L-arginine (L-NNA) and mefenamic acid (MA), which are specific inhibitors of NO and prostaglandin synthesis, respectively, elicited a significant reduction in basal diaphragmatic arteriolar diameter. A dramatic potentiation of the effect of each inhibitor was observed when both agents were applied simultaneously. ACh application induced a significant and dose-dependent increase in arteriolar diameter that was not significantly modified by the separate application of L-NNA or MA. Conversely, the simultaneous administration of L-NNA and MA almost completely prevented ACh-induced arteriolar dilatation. Dilatation in response to sodium nitroprusside was not significantly modified in the presence of both inhibitors. These results suggest that NO and prostaglandins act in concert to regulate basal diaphragmatic arteriolar tone and to mediate diaphragmatic arteriolar response to ACh.

Inhibition of nitric oxide synthase produces hypothermia and depresses lipopolysaccharide fever

1996 ◽  
Vol 271 (2) ◽  
pp. R333-R338 ◽  
Author(s):  
T. E. Scammell ◽  
J. K. Elmquist ◽  
C. B. Saper
Keyword(s):  
Nitric Oxide ◽  
Low Dose ◽  
Dependent Manner ◽  
Febrile Response ◽  
Bolus Intravenous Injection ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Dose Dependent ◽  
Higher Doses

The labile gas nitric oxide (NO) mediates a wide variety of thermoregulatory processes including vasomotor control, brown fat thermogenesis, and neuroendocrine regulation. Additionally, during endotoxemia, NO modulates the release of cytokines and hypothalamic peptides. To determine the role of NO in thermoregulation and fever, we intravenously injected the NO synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) and measured its effects on body temperature during normal thermoregulation and endotoxemia in awake, unrestrained rats. L-NAME produced a stereoselective, dose-dependent hypothermia that lasted up to 4 h after bolus intravenous injection. Intravenous lipopolysaccharide (LPS) produced fever in a dose-dependent manner, which was preceded by hypothermia at higher doses alpha-LPS. NOS inhibition reduced the febrile response to LPS and produced marked hypothermia with a low dose of LPS. These findings indicate that NO may play an important role in thermoregulation and suggest that NO is required for the production of fever.

Direct measurement of static chest wall compliance in animal and human neonates

1988 ◽  
Vol 65 (3) ◽  
pp. 1093-1098 ◽  
Author(s):  
G. M. Davis ◽  
A. L. Coates ◽  
A. Papageorgiou ◽  
M. A. Bureau
Keyword(s):  
Chest Wall ◽  
Face Mask ◽  
Premature Neonate ◽  
Lung Compliance ◽  
Pulmonary Mechanics ◽  
Chest Wall Compliance ◽  
Wall Compliance ◽  
The Mean ◽  
Dynamic Lung Compliance ◽  
Neonates And Infants

The measurement of pulmonary mechanics has been developed extensively for adults, and these techniques have been applied directly to neonates and infants. However, the compliant chest wall of the infant frequently predisposes to chest wall distortion, especially when there is a low dynamic lung compliance (CL,dyn). We describe a technique of directly measuring the static chest wall compliance (Cw,st), developed initially in the newborn lamb and subsequently applied to the premature neonate with chest wall distortion. The mean CL,dyn in seven intubated newborn lambs in normoxia was 2.45 +/- 0.41 ml.cmH2O-1.kg-1, whereas Cw,st was 11.81 +/- 0.25 ml.cmH2O-1.kg-1. These values did not change significantly in seven animals breathing through a tight-fitting face mask or with hypercapnia-induced tachypnea. For the eight premature infants the mean CL,dyn was 1.35 +/- 0.36 ml.cmH2O-1.kg-1, whereas the mean Cw,st was 3.16 +/- 1.01 ml.cmH2O-1.kg-1. This study shows that, under relaxed conditions when measurements of static compliance are performed, the chest wall is more compliant than the lung. The measurement of Cw,st may thus be used to determine the contribution of the respiratory musculature in stabilizing the chest wall.

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