| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Vol. 84, Issue 3, 809-814, March 1998
University of British Columbia Pulmonary Research Laboratory, St. Paul's Hospital, Vancouver, British Columbia, Canada V6Z 1Y6
 |
ABSTRACT |
|---|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
Endogenous nitric oxide (NO) influences acetylcholine-induced
bronchovascular dilation in sheep and is a mediator of the airway smooth muscle inhibitory nonadrenergic, noncholinergic neural response
in several species. This study was designed to determine the importance
of NO as a neurally derived modulator of ovine airway and bronchial
vascular smooth muscle. We measured the response of pulmonary
resistance (RL) and bronchial
blood flow (
br) to vagal stimulation
in 14 anesthetized, ventilated, open-chest sheep during
the following conditions: 1)
control; 2) infusion of the 
-agonist phenylephrine to reduce baseline br by
the same amount as would be produced by infusion of
N
-nitro-L-arginine
(L-NNA), a NO synthase
inhibitor; 3) infusion of
L-NNA
(10
2 M); and
4) after administration of atropine
(1.5 mg/kg). The results showed that vagal stimulation produced an
increase in RL and
br in periods 1, 2, and 3 (P < 0.01) that was not affected by
L-NNA. After
atropine was administered, there was no increase in
br or RL. In
vitro experiments on trachealis smooth muscle contracted with carbachol showed no effect of
L-NNA on neural relaxation but
showed a complete blockade with propranolol
(P < 0.01). In conclusion, the
vagally induced airway smooth muscle contraction and bronchial vascular
dilation are not influenced by NO, and the sheep's trachealis muscle,
unlike that in several other species, does not have inhibitory
nonadrenergic, noncholinergic innervation.
bronchial blood flow; pulmonary resistance; nitric oxide; nitric oxide synthase inhibitor; vagal stimulation; airway smooth muscle; electrical field stimulation
| |
INTRODUCTION |
|---|
|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
IN A PREVIOUS STUDY from our laboratory, Sasaki et al.
(12) have shown that acetylcholine (ACh) injected directly into the bronchial circulation of anesthetized sheep causes bronchoconstriction and an increase in bronchial arterial blood flow. The bronchial vascular dilation was mediated, in part, by release of nitric oxide
(NO) because inhibition of NO synthase (NOS) attenuated the dilator
response as well as decreasing baseline blood flow. The ACh-induced
bronchoconstriction was not, however, enhanced after NOS inhibition.
This suggests that when NO is released from the bronchial vasculature
it does not influence airway smooth muscle contraction. Another source
of NO, as a potential regulator of bronchial blood flow
(br) and airway tone, is nonadrenergic, noncholinergic (NANC) nerve endings (4).
The neurotransmitter that mediates the inhibitory NANC response of airway and vascular smooth muscle has been characterized as NO in a variety of species (1-4, 7, 14, 17). In addition, it has been shown that release of NO can modulate bronchoconstriction in some animals. For instance, inhibition of NOS causes an enhanced response to vagal stimulation in the guinea pig (3). Vagal nerve stimulation has been shown to cause bronchial vascular dilation in pigs (11) and cats (10). This vasodilatory effect was not blocked by administration of atropine in pigs (11) and was only partially inhibited by atropine in cats (10). This result suggests the presence of a NANC inhibitory system. As yet, the presence of a NANC inhibitory system has not been conclusively demonstrated in either airways or bronchial vasculature in the ovine lung. In 1982, Sheller and Brigham (13) showed that the adrenergic nervous system was an important inhibitory mechanism of airway smooth muscle contraction in sheep. However, because the role of NO as a neurotransmitter had not been described at that time, it was not possible to verify the mechanism of the observed residual nonadrenergic relaxation. Because NO has since been identified as the major NANC inhibitory mediator in the airways (4), we have assessed its importance as a neurally derived modulator of ovine airway smooth muscle tone in vitro and in vivo. In addition, we have determined whether NO contributes to the bronchial vascular dilation that is caused by vagal nerve stimulation in this species.
| |
METHODS |
|---|
|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
Intact Sheep
Surgical protocol. We studied 14 Dorset-cross rams (25-30 kg) that were placed in the supine position.
All studies were done according to the Canadian guidelines for the use and care of animals. Anesthesia was induced by injection of thiopental sodium (15-20 mg/kg iv). A tracheotomy tube was inserted, and the sheep were ventilated with 50% O2 and air at a tidal volume (VT) of 12-15 ml/kg and a rate of ~15 breaths/min. Anesthesia was maintained by using a continuous infusion of thiopental sodium (5-10 mg · kg1 · h1
iv).
A catheter was inserted in the left carotid artery to measure systemic
arterial blood pressure and to obtain blood samples for measurement of
arterial blood-gas tensions. With the use of fluoroscopy, we inserted a
thermistor-tipped, triple-lumen catheter into the right jugular vein
and advanced the catheter to the pulmonary artery for measurement of
pulmonary arterial and wedge pressure. Cardiac output was measured by
using the thermodilution technique. A double-lumen catheter was placed
in the superior vena cava for continuous infusion of the anesthetic
(proximal port) and administration of intravenous fluids and drugs
(distal port) as necessary. All vascular pressures were referenced to
the level of the left atrium. A 5-cm length of the right and left vagus
nerve was carefully exposed.
Sheep were paralyzed by intravenous injection of 2 mg pancuronium
bromide. The chest was then opened by a left thoracotomy incision
between the 5th and 6th ribs, and 3 cmH2O positive end-expiratory pressure was applied. To measure bronchial arterial blood flow, we
carefully exposed the bronchial artery. A 2-mm flow probe (Transonic Systems, Ithaca, NY) was placed around the bronchoesophageal artery. The probe was then connected to the flowmeter, and
br was recorded by using a low-pass-filter setting
of 10 Hz. A 5-Fr cobra catheter was introduced into the right femoral
artery. With the use of fluoroscopy and injection of small amounts of
radiocontrast material, we advanced the catheter so that the tip was in
the orifice of the bronchoesophageal artery. br was
recorded continuously during placement of the cobra catheter to ensure
that it was situated so that it did not alter the blood flow. To
prevent clotting in the cobra catheter and in the bronchial artery,
heparin (4,000 U) was given intravenously; this was supplemented by
giving 1,000 U every 2 h. All pressure and flow tracings were displayed
continuously on a video display unit and were recorded, as necessary,
by using a digital recording system (Ray Tech, Vancouver, BC, Canada).
As soon as an intravenous line was in place, ibuprofen
[-methyl-4-(2-methylpropyl)-benzeneacetic acid; 15 mg/kg in
0.5 M saline; Sigma Chemical, St. Louis, MO] was administered to
block any vasodilatory effects of prostaglandins. After surgery was completed, an intravenous bolus (2 mg/kg) of the 
-adrenergic blocker
DL-propranolol hydrochloride
[1-(isopropylamino)-3-(1-naphthyloxy)-2-propanolol; Sigma
Chemical] was administered, followed by a continuous
infusion of 20 µg · kg1 · min1
propranolol.
To measure lung resistance (RL,
cmH2O · l1 · s),
airflow was measured by using a Fleisch no. 1 pneumotachometer, and
tracheal pressure was measured from a side port (2 mm ID) of the
tracheostomy tube with a differential pressure transducer (model MP45;
Validyne, Northridge, CA). Because the chest was open, tracheal
pressure was compared with atmospheric pressure to give transpulmonary pressure (PL).
RL was calculated, using the
computer program ANADAT (RHT-InfoDat, Montreal, Canada), by multiple
linear-regression curve fitting of
PL = EV + RL · 
+ Po, where V is volume, E is lung elastance, is
airflow, and Po is a constant equal to positive end-expiratory pressure
of 3 cmH2O (8).
Experimental protocol.
When the sheep were stabilized, ~30 min after completion of the
surgical procedures, we recorded baseline measurements of cardiac
output, systemic arterial blood pressure, pulmonary arterial pressure,
br, arterial blood-gas tensions and
RL. Vagal stimulation was
applied during four different experimental conditions:
1) postvagotomy;
2) bronchial arterial infusion of
the -agonist phenylephrine (5 × 106 to 5 × 107 M);
3) bronchial arterial infusion of
the NOS inhibitor L-NNA (1 × 102 M); and
4) after administration of atropine
(atropine sulfate salt, 1.5 mg/kg; Sigma).
br, and
arterial blood-gas tensions (control) were recorded, a bilateral
vagotomy was performed. The cut ends of the nerves were coated in
mineral oil to keep them moist. We used a constant-current stimulator,
repetitive mode (5-10 s), and stimulated the nerve at a frequency
of 8 Hz and a pulse width of 2 ms. The duration of stimulation varied
between 3 and 20 s (compliance voltage of ~35 V), and
the current (0.4-4 A) was varied to give the greatest increase in
br associated with the least fall in systemic
arterial blood pressure (there was always 1 vagus that produced a
greater increase in br for a smaller fall in blood pressure). After the optimal response had been determined, all of the
stimulus settings remained the same for the rest of the experiment.
PERIOD 1: POSTVAGOTOMY.
Before the vagus nerve was stimulated, physiological measurements were
recorded as described above. The protocol for stimulation of the vagus
nerve was as follows: 15 s before stimulation, we started recording
measurements of blood pressure, br, and
RL. The vagus was stimulated by
using the optimal stimulator settings as described above, and the peak
increase in br was recorded. br
usually returned to the baseline value within 2-3 min after vagal
stimulation. After ~5 min, the vagus was stimulated again, and repeat
measurements of br were obtained to ensure
reproducibility of the response. Three such measurements were usually
made, and the average value of the closest two measurements was used in the data analysis.
PERIOD 2: INFUSION OF PHENYLEPHRINE.
Phenylephrine was given in 9 of the 14 sheep, because we knew, from
results of a previous study from our laboratory (12), that infusion of
L-NNA produces a consistent
decrease in baseline br. Therefore, to test whether
simple vasoconstriction with a contractile agonist would attenuate the
vasodilatory response to vagal stimulation, we gave sufficient
phenylephrine to decrease br by the same amount as
we anticipated would occur on infusion of
L-NNA. It usually took 5-10
min of infusion of phenylephrine to reduce br to
this anticipated level (~50% of the baseline value). The vagus was
then stimulated, and measurements were repeated.
PERIOD 3: INFUSION OF
L-NNA.
L-NNA
(102 M) was infused for 20 min via the cobra catheter into the bronchial artery, as previously
described (12). The infusion rate was set at one- tenth of the
br (2-3 ml/min) and adjusted at 5-min
intervals as br decreased. Infusion of
L-NNA was continued while
physiological parameters were recorded, the vagus was stimulated, and
measurements were repeated.
PERIOD 4: ATROPINE.
Atropine (1.5 mg/kg iv) was given as a bolus; after ~20 min, the
vagus was stimulated and recordings were made.
At the end of the experiment, the sheep were deeply anesthetized and
killed by intravascular injection of saturated potassium chloride.
Excised Airways
On the morning of the study, we obtained from the slaughterhouse six fresh lungs from Dorset-cross sheep (sheep weight, ~40 kg). Trachealis muscle segments were obtained by excising them from the cartilage and cutting them into strips ~3 mm wide and 15 mm long. The trachealis muscle strips were mounted under 2-g preload in a jacketed water bath and were incubated at 37°C in Krebs-Henseleit solution (composition in mM: 118.4 NaCl, 4.7 KCl, 1.2 KH2PO4, 2.5 CaCl2 · H2O, 25.0 NaHCO3, 1.2 MgSO4 · 7 H2O, 11.1 D-glucose) containing 5 µM indomethacin and continuously aerated with 5% CO2 in O2. After a 1-h equilibration period, frequency-response curves to electrical field stimulation were obtained by using platinum wire electrodes. Settings for the stimulator were based on the work of Kannan and Johnson (7) and were optimized for maximal responses with our apparatus. Settings were 70 V, 1-ms pulse duration, for 20 s at frequencies between 1 and 32 Hz. Contractile responses (force generated) were measured by Grass FTO3 transducers during the 20-s stimulation period and were recorded on Beckman chart recorders. The strips were incubated for 20 min in atropine (0.3 µM). Responses to 1, 4, 8, and 32 Hz were again obtained, with a 5-min period between each stimulation. The tissue was then washed once, and 5 µM carbachol was added to precontract the muscle. One segment of tissue was then incubated with NG-nitro-L-arginine (32 µM) for 30 min (tissue A), and a control tissue (tissue B) was incubated with Krebs-Henseleit solution. Relaxant responses to electrical field stimulation were then assessed at 1, 4, 8, and 32 Hz. Tissue A was then treated with 1 µM propranolol for 30 min; tissue B remained a control tissue and received an additional amount of Krebs-Henseleit solution. Repeat responses were obtained at 1, 4, 8, and 32 Hz. Tetrodotoxin (1 µM) was then added to the bath for 10 min, and responses were repeated, using the same frequencies as described above. Finally, theophylline (1 µM) was added to the bath to determine the maximal amount of smooth muscle relaxation. Whenever possible, duplicate tissues were studied, so that four tissues from each sheep were used.Data Analysis
Intact sheep.
The data were expressed as absolute values and as a
percentage of baseline. A paired
t-test was used to test whether there was a difference in br before and after vagotomy.
The responses to vagal stimulation were compared as absolute changes
and as percent changes during the four experimental periods. To test whether vagal stimulation increased br, bronchial
vascular resistance, and
RL, baseline and
peak br (ml/min), bronchial vascular resistance (mmHg · ml1 · min),
and RL
(cmH2O · l1 · s)
were analyzed by using a one-tailed, paired
t-test. A two-way analysis of variance
was used to compare baseline br and
RL in the four different
experimental periods (postvagotomy, phenylephrine, L-NNA, and after atropine).
After application of a square-root transformation of the data, the
absolute and percent increases in br and bronchial
vascular resistance produced by vagal stimulation during the four
experimental periods were analyzed by using a repeated-measures
analysis of variance with two repeating factors. The sequential
rejective Bonferroni procedure was used to correct for multiple
comparisons and multiple t-tests. A
corrected P value <0.05 was
considered to be significant.
Excised airways. Contractile responses of the trachealis muscle were expressed as percentage of the tension developed at 32 Hz (which was found to be maximal in preliminary experiments). Relaxation responses after electrical field stimulation were expressed as percentage of the maximal theophylline-induced relaxation. The effect of L-NNA, propranolol, and tetrodotoxin was assessed by using a repeated-measures analysis of variance. A P value <0.05 was considered significant.
| |
RESULTS |
|---|
|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
Intact Sheep
br decreased from 21.5 ± 10 (SD) to 16 ± 7 ml/min after vagotomy (P < 0.05).
Data for individual sheep for br (ml/min) obtained
just before (baseline) and at the peak response to vagal nerve
stimulation (peak) for the four experimental periods after vagotomy are
shown in Table 1. The
values (means ± SD) for br and bronchial vascular
resistance at baseline and in response to vagal stimulation are shown
in Table 2. Baseline values
of br measured during
periods 2, 3, and
4 (phenylephrine,
L-NNA, and atropine,
respectively) were all less (P < 0.01) than during period 1 (postvagotomy). There were no differences in baseline values of
br between periods 2, 3, and 4. In response
to vagal stimulation, there was an increase in br
(P < 0.01) in
periods 1, 2, and
3. After atropine, there was no
increase in br after vagal stimulation. The increase
in blood flow in response to vagal stimulation was greater in
period 1 than in
period 2 (P < 0.05) and
period 3 (P < 0.01). There was no difference
in the increase in br between
periods 2 and
3. When the increase in
br was expressed as a percentage of baseline, there
were no differences between periods 1, 2, and 3.
|
|
The values (means ± SD) for bronchial vascular resistance at
baseline and in response to vagal stimulation are shown for the four
experimental periods in Table 2. Data are expressed as
absolute values and as percent change. Because infusion of
phenylephrine and L-NNA produced
only a slight increase in baseline values of systemic arterial blood
pressure (1 ± 5 and 5 ± 14 mmHg, respectively), the
changes in bronchial vascular resistance were similar to the changes in
br.
Table 3 shows data (means ± SD) for
RL
(cmH2O · l1 · s)
obtained just before (baseline) and at the peak response to vagal nerve
stimulation (peak) as well as the absolute and percent changes from the
baseline value for the four experimental periods. There was no difference in baseline RL
for the four experimental periods. Vagal stimulation produced a small
increase in the absolute and percent increase in
RL in periods
1, 2, and 3, but there
was no change in RL after
administration of atropine. There was no difference in the absolute or
percentage increase in RL during
periods 1, 2, and
3.
|
Table 4 shows values (means ± SD) for hemodynamics,
arterial blood-gas tensions, br, and bronchial
vascular resistance. Measurements were obtained during stable periods.
There were no changes in pulmonary arterial pressure, cardiac output,
arterial CO2 tension, and arterial O2 tension
during the study. Blood pressure and br were lower
after vagotomy compared with prevagotomy and after administration of
L-NNA and after atropine
(P < 0.05). pH was
lower after vagotomy (P < 0.05) and
returned to prevagotomy values by the end of the experiment.
|
Excised Airways
Results, expressed as mean ± SE, are shown in Figs. 1 and 2. Atropine abolished the contractile response to electrical field stimulation in all tissues. When the stimulations were performed after carbachol administration, frequency-dependent relaxation responses were observed. These relaxation responses were not altered by prior incubation of the tissue in L-NNA (Fig. 1) but were completely abolished in tissues pretreated with 1 µM propranolol (Fig. 2) or tetrodotoxin (P < 0.01).
|
|
| |
DISCUSSION |
|---|
|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
The results of this study show that vagal stimulation in the sheep causes bronchoconstriction and bronchial arterial dilation in vivo. After cholinergic blockade, electrical field stimulation in vitro caused tracheal smooth muscle relaxation. These neural effects were not altered by NOS inhibitors, suggesting that NO is not mediating or influencing these responses. In contrast, the bronchial vascular dilation and the airway smooth muscle relaxation in vitro were completely blocked by administration of atropine and propranolol, respectively. These results imply that release of ACh mediates bronchial vascular dilation by a pathway that does not involve the generation of NO. In addition, these results show that the neural component of airway smooth muscle relaxation in sheep can be entirely explained by catecholamine release from autonomic nerve endings. It is apparent that these responses are different in the sheep from responses in several other species (1, 3, 4, 7, 17), thus emphasizing the differences between species in the neural control of airway and bronchial vascular smooth muscle.
Bronchial Vascular Smooth Muscle
The decrease inbr observed after vagotomy suggests
that intact vagal innervation may be important for maintaining normal bronchial vascular tone. The effects of NO inhibitors on bronchial vascular smooth muscle relaxation are complex. As has been previously shown in our laboratory (12), the administration of
L-NNA produces a substantial
fall in the baseline bronchial arterial blood flow; this makes it
difficult to interpret the comparison of subsequent vasodilatory
stimuli. In this study, vagal stimulation produced a significant
increase in bronchial arterial blood flow after vagotomy and
administration of L-NNA.
Although the absolute increase in blood flow produced by vagal
stimulation was attenuated by administration of
L-NNA, the percent
increase was not. However, because the baseline br
was considerably less after administration of
L-NNA, a comparison of the
absolute increase in br is not strictly
valid. To address this concern, we administered intra-arterial phenylephrine in a dosage sufficient to produce a comparable reduction in baseline bronchial arterial blood flow. In a previous study from
this laboratory (12), phenylephrine and
L-NNA were given to reduce
br by a similar amount before injection of ACh into the bronchial artery. Pretreatment with
L-NNA was shown to attenuate significantly both the absolute and the percent increases in
br compared with the increase after pretreatment with
phenylephrine. We interpreted the different responses to ACh to imply
that ACh caused the bronchial vascular dilation through release of NO. In the present study, the increase in br after vagal
stimulation seen after L-NNA was
compared with that seen after administration of phenylephrine. There
was no significant difference in the absolute and percent increases in
blood flow under these conditions. To the extent that there is not an
interaction of vagal stimulation with the vasoconstriction caused by
NOS inhibition or phenylephrine, these results suggest that inhibition
of NOS did not influence the vagally induced vasodilation and,
therefore, that NO was not an important mediator of the response.
There are at least three possible ways in which NO could be involved in bronchial vasodilation. First, postganglionic nerves innervating the bronchial vasculature (16) could contain NO as a neurotransmitter. Second, ACh released from postganglionic cholinergic nerves could release NO from tissue cells such as the bronchial vascular endothelium or smooth muscle. Third, NO could be acting at peribronchial ganglia, influencing postganglionic excitation. The fact that inhibition of NOS did not attenuate the bronchial vasodilation would seem to negate all three possible mechanisms. Only atropine completely attenuated the bronchial vasodilatory response. This result suggests that ACh, either directly or via an alternate pathway, is important in mediating this response.
Our results, relating to the effects of vagal nerve stimulation on bronchial arterial blood flow, are both in agreement with and at variance with the literature. Vagal nerve stimulation has been shown to cause bronchial vasodilation in cats and pigs (10, 11). However, in these species, the effect was not completely blocked by atropine. We cannot comment on the potential involvement of prostanoids in the in vivo airway or vascular responses, because the sheep in the present study were pretreated with ibuprofen in accordance with previous methodology (12). Because neurotransmitters released from vagal nerve endings may simultaneously affect bronchial vascular and airway smooth muscle tone, we also measured airway narrowing and tracheal smooth muscle contraction in the present studies.
Airway Smooth Muscle In Vivo
The NOS inhibitor L-NNA had no effect on the bronchoconstriction produced by vagal nerve stimulation, as measured by the change in RL. We had postulated that if vagal nerve stimulation caused release of NO, then attenuation of the NOS by L-NNA would cause enhanced bronchoconstriction. This negative in vivo finding is consistent with the in vitro studies that showed no evidence of a NANC inhibitory system.Airway Smooth Muscle In Vitro
The present results clearly show that there is no inhibitory NANC innervation of ovine trachealis muscle and that neurally induced relaxation is adrenergically mediated. A single inhibitory adrenergic innervation of airway smooth muscle appears to be unique to sheep, compared with all the other species studied to date. There is considerable evidence to suggest that NO released from inhibitory NANC nerves is the principal neural mediator of airway smooth muscle relaxation in several species (1, 4, 6, 7, 17). NO accounts for the inhibitory NANC response in peripheral and central human airways (1, 5), and results from in vitro studies of guinea pig trachealis muscle show that NO accounts for ~50% of the inhibitory NANC response (9, 16). Similarly, NO seems to be the principal inhibitory NANC mediator in pig tracheal smooth muscle because neural relaxation was completely inhibited after administration of L-NNA and was reversed by L-arginine, a substrate for NOS (7). Similarly, NO has been shown to be the primary mediator of NANC relaxation in the cat trachealis muscle (6).In 1982, Sheller and Brigham (13) demonstrated the presence of neural
-adrenergic airway smooth muscle relaxation in sheep. They found
that electrical field stimulation in the presence of atropine produced
a frequency-dependent relaxation of serotonin-induced tension in
tracheal segments and bronchial rings. The relaxation was diminished
after administration of propranolol
(106 M) or guanethidine
(105 M). They could not
assess the contribution of NO, because at that time it had not been
identified as a neurotransmitter. The results of the present study
confirm the presence of a dominant -adrenergic relaxation of ovine
airway smooth muscle and demonstrate that NO is not involved in this
response. Although we did not systematically study bronchi in the
sheep, we did examine several specimens and found similar results.
In conclusion, the results of the present study indicate significant interspecies differences in the neurotransmitters that mediate airway smooth muscle and bronchial smooth muscle relaxation.
| |
ACKNOWLEDGEMENTS |
|---|
Support for this study was provided in part by the Heart and Stroke Foundation of British Columbia and Yukon. K. McKay was the recipient of a traveling fellowship from the Medical Foundation of the University of Sydney, Australia.
| |
FOOTNOTES |
|---|
Address for correspondence: E. Baile, St. Paul's Hospital, 1081 Burrard St., Vancouver, BC, Canada V6Z 1Y6 (E-mail: lbaile{at}prl.pulmonary.ubc.ca).
Received 18 April 1997; accepted in final form 29 October 1997.
| |
REFERENCES |
|---|
|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
1.
Bai, T. R.,
and
A. M. Bramley.
Effect of an inhibitor of nitric oxide synthase on neural relaxation of human bronchi.
Am. J. Physiol.
264 (Lung Cell. Mol. Physiol. 8):
L425-L430,
1993
2.
Belvisi, M. G.,
and
T. R. Bai.
Inhibitory nonadrenergic, noncholinergic innervation of airways smooth muscle: role of nitric oxide.
In: Airways Smooth Muscle Structure, Innervation and Neutrotransmission, edited by D. Raeburn,
and M. A. Giembycz. Basel: Birkhäuser, 1994, p. 157-187.
3.
Belvisi, M. G.,
C. D. Stretton,
and
P. J. Barnes.
Nitric oxide as an endogenous modulator of cholinergic neurotransmission in guinea-pig airways.
Eur. J. Pharmacol.
198:
219-221,
1991[Medline].
4.
Belvisi, M. G.,
C. D. Stretton,
M. Yacoub,
and
P. J. Barnes.
Nitric oxide is the endogenous neurotransmitter of bronchodilator nerves in humans.
Eur. J. Pharmacol.
210:
221-222,
1992[Medline].
5.
Ellis, J. L.,
and
B. J. Undem.
Inhibition by L-NG-nitro-L-arginine of nonadrenergic noncholinergic mediated relaxations of human isolated central and peripheral airways.
Am. Rev. Respir. Dis.
146:
1543-1547,
1992[Medline].
6.
Fisher, J. T.,
J. W. Anderson,
and
M. A. Waldron.
Nonadrenergic noncholinergic neurotransmitter of feline trachealis.
J. Appl. Physiol.
74:
31-39,
1993
7.
Kannan, M. S.,
and
D. E. Johnson.
Nitric oxide mediates the neural nonadrenergic, noncholinergic relaxation of pig tracheal smooth muscle.
Am. J. Physiol.
262 (Lung Cell. Mol. Physiol. 6):
L511-L514,
1992
8.
Lauzon, A. M.,
and
J. H. T. Bates.
Estimation of time-varying respiratory mechanical parameters by recursive least squares.
J. Appl. Physiol.
71:
1159-1165,
1991
9.
Li, C. G.,
and
M. J. Rand.
Evidence that part of the NANC relaxant response of guinea-pig trachea to electrical field stimulation is mediated by nitric oxide.
Br. J. Pharmacol.
102:
91-94,
1991[Medline].
10.
Martling, C.-R.,
B. Gazelius,
and
J. M. Lundberg.
Nervous control of tracheal blood flow in the cat measured by the laser Doppler technique.
Acta Physiol. Scand.
130:
409-417,
1987[Medline].
11.
Matran, K. A.,
C.-R. Martling,
J. S. Lacroix,
and
J. M. Lundberg.
Vagally mediated vasodilation by motor sensory nerves in the tracheal and bronchial circulation of the pig.
Acta Physiol. Scand.
135:
29-37,
1989[Medline].
12.
Sasaki, F.,
P. Paré,
D. Ernest,
T. Bai,
L. Verburgt,
R. March,
and
E. Baile.
Endogenous nitric oxide influences acetylcholine-induced bronchovascular dilation in sheep.
J. Appl. Physiol.
78:
539-545,
1995
13.
Sheller, J. R.,
and
K. L. Brigham.
Bronchomotor responses of isolated sheep airways to electrical field stimulation.
J. Appl. Physiol.
53:
1088-1093,
1982
14.
Toda, N.,
K. Ayajiki,
and
T. Okamura.
Cerebroarterial relaxations mediated by nitric oxide derived from endothelium and vasodilator nerve.
J. Vasc. Res.
30:
61-67,
1993[Medline].
15.
Tucker, J. F.,
S. R. Brane,
L. Charalambons,
A. J. Hobbs,
and
A. Gibson.
L-NG-nitro-arginine inhibits non-adrenergic, non-cholinergic relaxations of guinea pig isolated tracheal smooth muscle.
Br. J. Pharmacol.
100:
663-664,
1990[Medline].
16.
Widdicombe, J. G. Neuroregulation of the nose and
bronchi. Clin. Exp. Allergy 6, Suppl. 3: 32-35, 1996.
17.
Yu, M.,
Z. Wang,
N. E. Robinson,
and
P. H. Leblanc.
Inhibitory nerve distribution and mediation of NANC relaxation by nitric oxide in horse airways.
J. Appl. Physiol.
76:
339-344,
1994
This article has been cited by other articles:
|
|
 |
|
  F. L. M. Ricciardolo, P. J. Sterk, B. Gaston, and G. Folkerts Nitric Oxide in Health and Disease of the Respiratory System Physiol Rev, July 1, 2004; 84(3): 731 - 765. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F L M Ricciardolo Multiple roles of nitric oxide in the airways Thorax, February 1, 2003; 58(2): 175 - 182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. E. Pisarri, M. P. Zimmerman, T. E. Adrian, J. C. G. Coleridge, and H. M. Coleridge Bronchial vasodilator pathways in the vagus nerve of dogs J Appl Physiol, January 1, 1999; 86(1): 105 - 113. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
