Role of nitric oxide in the airway response to exercise in healthy and asthmatic subjects

2001 ◽  
Vol 90 (2) ◽  
pp. 586-592 ◽  
Author(s):  
H. W. F. M. De Gouw ◽  
S. J. Marshall-Partridge ◽  
H. Van der Veen ◽  
J. G. Van den Aardweg ◽  
P. S. Hiemstra ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Healthy Subjects ◽  
Geometric Mean ◽  
No Synthase ◽  
Bicycle Ergometry ◽  
Significant Difference ◽  
Airway Response ◽  
Exercise Induced ◽  
Response To Exercise

A role of nitric oxide (NO) has been suggested in the airway response to exercise. However, it is unclear whether NO may act as a protective or a stimulatory factor. Therefore, we examined the role of NO in the airway response to exercise by using N-monomethyl-l-arginine (l-NMMA, an NO synthase inhibitor), l-arginine (the NO synthase substrate), or placebo as pretreatment to exercise challenge in 12 healthy nonsmoking, nonatopic subjects and 12 nonsmoking, atopic asthmatic patients in a double-blind, crossover study. Fifteen minutes after inhalation of l-NMMA (10 mg),l-arginine (375 mg), or placebo, standardized bicycle ergometry was performed for 6 min using dry air, while ventilation was kept constant. The forced expiratory volume in 1-s response was expressed as area under the time-response curve (AUC) over 30 min. In healthy subjects, there was no significant change in AUC betweenl-NMMA and placebo treatment [28.6 ± 17.0 and 1.3 ± 20.4 (SE) for placebo and l-NMMA, respectively, P = 0.2]. In the asthmatic group, l-NMMA and l-arginine induced significant changes in exhaled NO ( P < 0.01) but had no significant effect on AUC compared with placebo (geometric mean ± SE: −204.3 ± 1.5, −186.9 ± 1.4, and −318.1 ± 1.2% · h for placebo,l-NMMA, and l-arginine, respectively, P > 0.2). However, there was a borderline significant difference in AUC between l-NMMA and l-arginine treatment ( P = 0.052). We conclude that modulation of NO synthesis has no effect on the airway response to exercise in healthy subjects but that NO synthesis inhibition slightly attenuates exercise-induced bronchoconstriction compared with NO synthase substrate supplementation in asthma. These data suggest that the net effect of endogenous NO is not inhibitory during exercise-induced bronchoconstriction in asthma.

Role of neutral endopeptidase in exercise-induced bronchoconstriction in asthmatic subjects

1996 ◽  
Vol 81 (2) ◽  
pp. 673-678 ◽  
Author(s):  
H. W. de Gouw ◽  
Z. Diamant ◽  
E. A. Kuijpers ◽  
J. K. Sont ◽  
P. J. Sterk
Keyword(s):  
Recovery Period ◽  
Neutral Endopeptidase ◽  
Bicycle Ergometer ◽  
Forced Expiratory Volume ◽  
Double Blind ◽  
Airway Response ◽  
Membrane Bound ◽  
Exercise Induced ◽  
Response To Exercise

The membrane-bound metalloproteinase, neutral endopeptidase (NEP), is a degrading enzyme of both bronchoconstrictor and bronchodilator peptides within the airways. To examine the role of NEP in exercise-induced bronchoconstriction (EIB) in asthmatic subjects, we used inhaled thiorphan, a NEP inhibitor, as pretreatment to a 6-min standardized exercise challenge. Thirteen clinically stable asthmatic subjects participated in this double-blind, placebo-controlled, crossover study that was performed on 2 days separated by 48 h. Thiorphan was administered by two inhalations of 0.5 ml containing 1.25 mg/ml. Subsequently, exercise was performed on a bicycle ergometer at 40–50% of predicted maximal voluntary ventilation while inhaling dry air (20 degrees C, relative humidity 6%). The airway response to exercise was measured by forced expiratory volume in 1 s (FEV1) every 3 min, up to 30 min postexercise challenge, and was expressed both as the maximal percent fall in FEV1 from baseline and as the area under the time-response curve (AUC) (0–30 min). The acute effects of both pretreatments on baseline FEV1 were not different (P > 0.2), neither was there any difference in maximal percent fall in FEV1 between thiorphan and placebo (P > 0.7). However, compared with placebo, thiorphan reduced the AUC by, on average, 26% [AUC (0–30 min, +/-SE): 213.6 +/- 47.7 (thiorphan) and 288.6 +/- 46.0%fall.h (placebo); P = 0.047]. These data indicate that NEP inhibition by thiorphan reduces EIB during the recovery period. This suggests that bronchodilator NEP substrates, such as vasoactive intestinal polypeptide or atrial natriuretic peptide, modulate EIB in patients with asthma.

scholarly journals Blockade of neuronal nitric oxide synthase alters the baroreflex control of heart rate in the rabbit

1998 ◽  
Vol 274 (1) ◽  
pp. R181-R186 ◽  
Author(s):  
Hiroshi Murakami ◽  
Jun-Li Liu ◽  
Hirohito Yoneyama ◽  
Yasuhiro Nishida ◽  
Kenji Okada ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heart Rate ◽  
No Synthase ◽  
Baroreflex Control ◽  
Neuronal No Synthase ◽  
Significant Difference ◽  
Before And After ◽  
Synthase Inhibitor ◽  
Oxide Synthase

In previous studies we used N G-nitro-l-arginine (l-NNA) to investigate the role of nitric oxide (NO) in baroreflex control of heart rate (HR) and renal sympathetic nerve activity (RSNA).l-NNA increased resting mean arterial pressure (MAP), decreased HR, and did not change or slightly decreased RSNA. These changes complicated the assessment of the central effects of NO on the baroreflex control of HR and RSNA. Therefore, in the present study the effects of the relatively selective neuronal NO synthase inhibitor 7-nitroindazole (7-NI) on the baroreflex control of HR and RSNA were investigated in rabbits. Intraperitoneal injection of 7-NI (50 mg/kg) had no effect on resting HR, MAP, or RSNA. 7-NI significantly reduced the lower plateau of the HR-MAP baroreflex curve from 140 ± 4 to 125 ± 4 and from 177 ± 10 to 120 ± 9 beats/min in conscious and anesthetized preparations, respectively ( P < 0.05). In contrast, there was no significant difference in the RSNA-MAP curves before and after 7-NI administration in conscious or anesthetized preparations. These data suggest that blockade of neuronal NO synthase influences baroreflex control of HR but not of RSNA in rabbits.

Role of the nitric oxide pathway in hypoxia-induced hypothermia of rats

1997 ◽  
Vol 273 (3) ◽  
pp. R967-R971 ◽  
Author(s):  
L. G. Branco ◽  
E. C. Carnio ◽  
R. C. Barros
Keyword(s):  
Nitric Oxide ◽  
Body Temperature ◽  
No Synthase ◽  
Regulatory Mechanisms ◽  
Induced Hypothermia ◽  
The Third ◽  
Significant Difference ◽  
Before And After ◽  
Nitric Oxide Pathway

Hypothermia is a response to hypoxia that occurs in organisms ranging from protozoans to mammals, but very little is known about the mechanisms involved. Recently, the NO pathway has been suggested to be involved in thermoregulation. In the present study, we assessed the participation of nitric oxide in hypoxia-induced hypothermia by means of NO synthase inhibition using NG-nitro-L-arginine methyl ester (L-NAME). The rectal temperature of awake, unrestrained rats was measured before and after hypoxia or L-NAME injection or both treatments together. Control animals received saline injections of the same volume. We observed a significant (P < 0.05) reduction in body temperature of 1.32 +/- 0.36 degrees C after hypoxia (7% inspired O2) and of 0.96 +/- 0.42 degree C after L-NAME (30 mg/kg body wt) injected intravenously. When the two treatments were combined, no significant difference in body temperature was observed. To assess the role of central thermo-regulatory mechanisms, a smaller dose of L-NAME (1 mg/kg) was injected into the third cerebral ventricle or intravenously. Intracerebroventricular injection of L-NAME caused an increase in body temperature, but when L-NAME was combined with hypoxia (7% inspired O2) no change in body temperature was observed. Intravenous injection of 1 mg/kg L-NAME had no effect. The data indicate that NO plays a major role in hypoxia-induced hypothermia at central rather than peripheral sites.

Skin Blood Flow Responses to Acetylcholine, Local Heating, and to 60% VO2max exercise with and without Nitric Oxide inhibition, in Boys vs. Girls

2021 ◽  
pp. 1-9
Author(s):  
Raffaele Joseph Massarotto ◽  
Gary J. Hodges ◽  
Alexandra Woloschuk ◽  
Deborah D. O’Leary ◽  
Raffy Dotan ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Methyl Ester ◽  
Skin Blood Flow ◽  
Local Heating ◽  
Local Heat ◽  
Exercise Induced ◽  
Oxide Synthase ◽  
Response To Exercise

Purpose: To determine sex-related differences in the skin blood flow (SkBF) response to exercise, local heating, and acetylcholine (ACh) in children, and to assess nitric oxide contribution to the SkBF response. Methods: Forearm SkBF during local heating (44°C), ACh iontophoresis, and exercise (30-min cycling and 60% of maximum oxygen consumption) was assessed, using laser Doppler fluxmetry, in 12 boys and 12 girls (7–13 y old), with and without nitric oxide synthase inhibition, using Nω-nitro-L-arginine methyl ester iontophoresis. Results: Local-heating-induced and ACh-induced SkBF increase were not different between boys and girls (local heating: 1445% [900%] and 1432% [582%] of baseline, P = .57; ACh: 673% [434%] and 558% [405%] of baseline, respectively, P = .18). Exercise-induced increase in SkBF was greater in boys than girls (528% [290%] and 374% [192%] of baseline, respectively, P = .03). Nω-nitro-L-arginine methyl ester blunted the SkBF response to ACh and during exercise (P < .001), with no difference between sexes. Conclusion: SkBF responses to ACh and local heat stimuli were similar in boys and girls, while the increase in SkBF during exercise was greater in boys. The apparent role of nitric oxide was not different between boys and girls. It is suggested that the greater SkBF response in boys during exercise was related to greater relative heat production and dissipation needs at this exercise intensity. The response to body size-related workload should be further examined.

Systemic and regional hemodynamics after nitric oxide synthase inhibition: role of a neurogenic mechanism

1994 ◽  
Vol 267 (1) ◽  
pp. R84-R88 ◽  
Author(s):  
M. Huang ◽  
M. L. Leblanc ◽  
R. L. Hester
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Cardiac Output ◽  
No Synthase ◽  
Before And After ◽  
Regional Hemodynamics ◽  
Autonomic Blockade ◽  
Infusion Of Norepinephrine ◽  
Oxide Synthase

The study tested the hypothesis that the increase in blood pressure and decrease in cardiac output after nitric oxide (NO) synthase inhibition with N omega-nitro-L-arginine methyl ester (L-NAME) was partially mediated by a neurogenic mechanism. Rats were anesthetized with Inactin (thiobutabarbital), and a control blood pressure was measured for 30 min. Cardiac output and tissue flows were measured with radioactive microspheres. All measurements of pressure and flows were made before and after NO synthase inhibition (20 mg/kg L-NAME) in a group of control animals and in a second group of animals in which the autonomic nervous system was blocked by 20 mg/kg hexamethonium. In this group of animals, an intravenous infusion of norepinephrine (20-140 ng/min) was used to maintain normal blood pressure. L-NAME treatment resulted in a significant increase in mean arterial pressure in both groups. L-NAME treatment decreased cardiac output approximately 50% in both the intact and autonomic blocked animals (P < 0.05). Autonomic blockade alone had no effect on tissue flows. L-NAME treatment caused a significant decrease in renal, hepatic artery, stomach, intestinal, and testicular blood flow in both groups. These results demonstrate that the increase in blood pressure and decreases in cardiac output and tissue flows after L-NAME treatment are not dependent on a neurogenic mechanism.

scholarly journals The role of nitric oxide synthase in exercise induced changes in endothelial progenitor cell number

2006 ◽  
Vol 20 (4) ◽  
Author(s):  
Patrick Nicholas Colleran ◽  
Miles A. Tanner ◽  
Shena L. Latcham ◽  
Sara L. Collier ◽  
M. Harold Laughlin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Endothelial Progenitor Cell ◽  
Progenitor Cell ◽  
Cell Number ◽  
Endothelial Progenitor ◽  
Exercise Induced ◽  
Induced Changes ◽  
Oxide Synthase

Role of nitric oxide in exercise-induced vasodilation in man

Life Sciences ◽  
1998 ◽  
Vol 62 (11) ◽  
pp. 1035-1042 ◽  
Author(s):  
Jeanette Koller-Strametz ◽  
Bettina Matulla ◽  
Michael Wolzt ◽  
Markus Müller ◽  
Jesusa Entlicher ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Exercise Induced

Release of nitric oxide and prostaglandin H2 to acetylcholine in skeletal muscle venules

1997 ◽  
Vol 272 (6) ◽  
pp. H2541-H2546 ◽  
Author(s):  
G. Dornyei ◽  
G. Kaley ◽  
A. Koller
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Perfusion Pressure ◽  
Thromboxane A2 ◽  
No Synthase ◽  
Gracilis Muscle ◽  
Vasoactive Agents ◽  
Before And After ◽  
Higher Doses

The role of endothelium in regulating venular resistance is not well characterized. Thus we aimed to elucidate the endothelium-derived factors involved in the mediation of responses of rat gracilis muscle venules to acetylcholine (ACh) and other vasoactive agents. Changes in diameter of perfusion pressure (7.5 mmHg)- and norepinephrine (10(-6) M)-constricted venules (approximately 225 microns in diam) to cumulative doses of ACh (10(-9) to 10(-4) M) and sodium nitroprusside (SNP, 10(-9) to 10(-4) M), before and after endothelium removal or application of various inhibitors, were measured. Lower doses of ACh elicited dilations (up to 42.1 +/- 4.7%), whereas higher doses of ACh resulted in smaller dilations or even constrictions. Endothelium removal abolished both ACh-induced dilation and constriction. In the presence of indomethacin (2.8 x 10(-5) M), a cyclooxygenase blocker, or SQ-29548 (10(-6) M), a thromboxane A2-prostaglandin H2 (PGH2) receptor antagonist, higher doses of ACh caused further dilation (up to 72.7 +/- 7%) instead of constriction. Similarly, lower doses of arachidonic acid (10(-9) to 10(-6) M) elicited dilations that were diminished at higher doses. These reduced responses were, however, reversed to substantial dilation by SQ-29548. The nitric oxide (NO) synthase blocker, N omega-nitro-L-arginine (L-NNA, 10(-4) M), significantly reduced the dilation to ACh (from 30.6 +/- 5.5 to 5.4 +/- 1.4% at 10(-6) M ACh). In contrast, L-NNA did not affect dilation to SNP. Thus ACh elicits the release of both NO and PGH2 from the venular endothelium.

Predominant site of flow limitation and mechanisms of postexertional asthma

1977 ◽  
Vol 42 (5) ◽  
pp. 746-752 ◽  
Author(s):  
E. R. McFadden ◽  
R. H. Ingram ◽  
R. L. Haynes ◽  
J. J. Wellman
Keyword(s):  
Airway Obstruction ◽  
Physical Exertion ◽  
Anticholinergic Agent ◽  
Disodium Cromoglycate ◽  
Flow Limitation ◽  
Before And After ◽  
Large Airways ◽  
Airway Response ◽  
Exercise Induced ◽  
Response To Exercise

To determine if a relationship existed between the site of airway obstruction and the mechanisms of exercise-induced asthma, we studied the predominant site of flow limitation, as determined by the mid-vital capacity ratios of maximal expiratory flow with air (Vmax air) and 80% helium-20% oxygen (Vmax He-O2), before and after physical exertion in 12 asthmatics. These observations were then related to the effects seen after vagal blockade and inhibition of mediator release. Five subjects increased Vmax He-O2/Vmax air ratios suggesting that the predominant site of flow limitation was in large airways. This group had their postexercise bronchospasm abolished by pretreatment with an anticholinergic agent. Seven subjects decreased their flow ratios indicating predominant small airway obstruction. Anticholinergic agents, although producing bronchodilation, did not alter their bronchospastic response to exercise. However, pretreatment with disodium cromoglycate did significantly diminish the response of this group. Thus the airway response to exercise in asthmatics is heterogeneous in terms of predominant site of flow limitation and this factor appears to relate to mechanisms.

Sign in / Sign up

Export Citation Format

Share Document