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.

scholarly journals Role of nitric oxide in systemic vasopressin-induced hypothermia

1998 ◽  
Vol 275 (4) ◽  
pp. R937-R941 ◽  
Author(s):  
Alexandre A. Steiner ◽  
Evelin C. Carnio ◽  
José Antunes-Rodrigues ◽  
Luiz G. S. Branco
Keyword(s):  
Nitric Oxide ◽  
Intravenous Injection ◽  
Induced Hypothermia ◽  
Basal Body Temperature ◽  
Systemic Injection ◽  
The Third ◽  
Before And After ◽  
Injection Control ◽  
Synthase Inhibitor

It has been reported that arginine vasopressin (AVP) plays a thermoregulatory action, but very little is known about the mechanisms involved. In the present study, we tested the hypothesis that nitric oxide (NO) plays a role in systemic AVP-induced hypothermia. Rectal temperature was measured before and after AVP, AVP blocker, or N G-nitro-l-arginine methyl ester (l-NAME; NO synthase inhibitor) injection. Control animals received saline injections of the same volume. The basal body temperature (Tb) measured in control animals was 36.53 ± 0.08°C. We observed a significant ( P < 0.05) reduction in Tb to 35.44 ± 0.19°C after intravenous injection of AVP (2 μg/kg) and to 35.74 ± 0.10°C after intravenous injection ofl-NAME (30 mg/kg). The systemic injection of the AVP blocker [β-mercapto-β,β-cyclopentamethylenepropionyl1, O-Et-Tyr2,Val4,Arg8]vasopressin (10 μg/kg) caused a significant increase in Tb to 37.33 ± 0.23°C, indicating that AVP plays a tonic role by reducing Tb. When the treatments with AVP and l-NAME were combined, systemically injected l-NAME blunted AVP-induced hypothermia. To assess the role of central thermoregulatory mechanisms, a smaller dose ofl-NAME (1 mg/kg) was injected into the third cerebral ventricle. Intracerebroventricular injection ofl-NAME caused an increase in Tb, but when intracerebroventricular l-NAME was combined with systemic AVP injection (2 μg/kg), no change in Tb was observed. The data indicate that central NO plays a major role mediating systemic AVP-induced hypothermia.

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.

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.

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.

Effect of nitric oxide synthase inhibition on hypercapnia-induced hypothermia and hyperventilation

1998 ◽  
Vol 85 (3) ◽  
pp. 967-972 ◽  
Author(s):  
Renata C. H. Barros ◽  
Luiz G. S. Branco
Keyword(s):  
Nitric Oxide ◽  
Oxygen Consumption ◽  
Body Temperature ◽  
Respiratory Function ◽  
Breathing Pattern ◽  
Ventilatory Response ◽  
No Synthase ◽  
Induced Hypothermia ◽  
Control Situation ◽  
Oxide Synthase

Hypercapnia elicits hypothermia in a number of vertebrates, but the mechanisms involved are not well understood. In the present study, we assessed the participation of the nitric oxide (NO) pathway in hypercapnia-induced hypothermia and hyperventilation by means of NO synthase inhibition by using N ω-nitro-l-arginine (l-NNA). Measurements of ventilation, body temperature, and oxygen consumption were performed in awake unrestrained rats before and afterl-NNA injection (intraperitoneally) and l-NNA injection followed by hypercapnia (5% CO2). Control animals received saline injections. l-NNA altered the breathing pattern during the control situation but not during hypercapnia. A significant ( P < 0.05) drop in body temperature was measured after bothl-NNA (40 mg/kg) and 5% inspired CO2, with a drop in oxygen consumption in the first situation but not in the second. Hypercapnia had no effect onl-NNA-induced hypothermia. The ventilatory response to hypercapnia was not changed byl-NNA, even thoughl-NNA caused a drop in body temperature. The present data indicate that the two responses elicited by hypercapnia, i.e., hyperventilation and hypothermia, do not share NO as a common mediator. However, thel-arginine-NO pathway participates, although in an unrelated way, in respiratory function and thermoregulation.

Microsphere-induced bronchial artery vasodilation: role of adenosine, prostacyclin, and nitric oxide

1998 ◽  
Vol 274 (3) ◽  
pp. H760-H768 ◽  
Author(s):  
David B. Pearse ◽  
Thomas E. Dahms ◽  
Elizabeth M. Wagner
Keyword(s):  
Nitric Oxide ◽  
Bronchial Artery ◽  
No Synthase ◽  
Blood Samples ◽  
Adenosine Release ◽  
Adenosine Receptor Antagonist ◽  
Adenosine Uptake ◽  
Before And After ◽  
Synthase Inhibitor

We previously found that injection of 15-μm microspheres into the bronchial artery of sheep decreased bronchial artery resistance. This effect was inhibited partially by indomethacin or 8-phenyltheophylline, suggesting that microspheres caused release of a dilating prostaglandin and adenosine. To identify the prostaglandin and confirm adenosine release, we perfused the bronchial artery in anesthetized sheep. In 12 sheep, bronchial artery blood samples were obtained before and after the infusion of 1 × 106microspheres or microsphere diluent into the bronchial artery. Microspheres, but not diluent, decreased bronchial artery resistance by 40% and increased bronchial artery plasma 6-ketoprostaglandin F1α (194.7 ± 45.0 to 496.5 ± 101.3 pg/ml), the stable metabolite of prostacyclin, and prostaglandin (PG) F2α (28.1 ± 4.4 to 46.2 ± 9.7 pg/ml). There were no changes in PGD2, PGE2, thromboxane B2, adenosine, inosine, or hypoxanthine. Pretreatment with dipyridamole, an adenosine uptake inhibitor, did not affect bronchial artery nucleoside concentrations ( n = 7). Microsphere-induced vasodilation was not enhanced by dipyridamole ( n = 9) and was not inhibited by either the adenosine receptor antagonist xanthine amine congener ( n = 4) or the nitric oxide (NO) synthase inhibitor N G-monomethyl-l-arginine ( n = 8). These results do not support a role for either adenosine or NO and suggest that microspheres caused bronchial artery vasodilation through release of prostacylin and an unidentified vasodilator.

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.

Endogenous nitric oxide modulates responses of tissue and airway resistance to vagal stimulation in piglets

2002 ◽  
Vol 93 (2) ◽  
pp. 450-456 ◽  
Author(s):  
Mohammad Y. Khassawneh ◽  
Ismail A. Dreshaj ◽  
Shijian Liu ◽  
Chung-Ho Chang ◽  
Musa A. Haxhiu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Airway Resistance ◽  
Vagal Stimulation ◽  
No Synthase ◽  
Excitatory Response ◽  
Tissue Resistance ◽  
Before And After ◽  
Endogenous Nitric Oxide ◽  
Cholinergic Effects

The role of endogenous nitric oxide (NO) in modulating the excitatory response of distal airways to vagal stimulation is unknown. In decerebrate, ventilated, open-chest piglets aged 3–10 days, lung resistance (Rl) was partitioned into tissue resistance (Rti) and airway resistance (Raw) by using alveolar capsules. Changes in Rl, Rti, and Raw were evaluated during vagal stimulation at increasing frequency before and after NO synthase blockade with N ω-nitro-l-arginine methyl ester (l-NAME). Vagal stimulation increased Rl by elevating both Rti and Raw. NO synthase blockade significantly increased baseline Rti, but not Raw, and significantly augmented the effects of vagal stimulation on both Rti and Raw. Vagal stimulation also resulted in a significant increase in cGMP levels in lung tissue before, but not after, l-NAME infusion. In seven additional piglets after Rl was elevated by histamine infusion in the presence of cholinergic blockade with atropine, vagal stimulation failed to elicit any change in Rl, Rti, or Raw. Therefore, endogenous NO not only plays a role in modulating baseline Rti, but it opposes the excitatory cholinergic effects on both the tissue and airway components of Rl. We speculate that activation of the NO/cGMP pathway during cholinergic stimulation plays an important role in modulating peripheral as well as central contractile elements in the developing lung.

Differential effects of l-NAME on rat venular hydraulic conductivity

2000 ◽  
Vol 279 (4) ◽  
pp. H2017-H2023 ◽  
Author(s):  
Rolando E. Rumbaut ◽  
Jianjie Wang ◽  
Virginia H. Huxley
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Methyl Ester ◽  
Hydraulic Conductivity ◽  
No Synthase ◽  
Vascular Effects ◽  
Nos Inhibitors ◽  
Before And After ◽  
Nos Inhibitor

The role of nitric oxide (NO) in microvascular permeability remains unclear because both increases and decreases in permeability by NO synthase (NOS) inhibitors have been reported. We sought to determine whether blood-borne constituents modify venular permeability responses to the NOS inhibitor N G-nitro-l-arginine methyl ester (l-NAME). We assessed hydraulic conductivity ( L p) of pipette-perfused rat mesenteric venules before and after exposure to 10−4 M l-NAME. In the absence of blood-borne constituents, l-NAME reduced L p by nearly 50% (from a median of 2.4 × 10−7cm · s−1 · cmH2O−1, n = 17, P < 0.001). The reduction in L p by l-NAME was inhibited by a 10-fold molar excess of l-arginine but notd-arginine ( n = 6). In a separate group of venules, blood flow was allowed to resume during exposure tol-NAME. In vessels perfused by blood duringl-NAME exposure, L p increased by 78% (from 1.4 × 10−7cm · s−1 · cmH2O−1, n = 10, P < 0.01). N G-nitro-d-arginine methyl ester did not affect L p in either of the two groups. These data imply that NO has direct vascular effects on permeability that are opposed by secondary changes in permeability mediated by blood-borne constituents.

Role of the Nitric Oxide Pathway in κ-Opioid-Induced Hypothermia in Rats

2002 ◽  
Vol 303 (1) ◽  
pp. 375-378 ◽  
Author(s):  
Khalid Benamar ◽  
Ellen B. Geller ◽  
Martin W. Adler
Keyword(s):  
Nitric Oxide ◽  
Induced Hypothermia ◽  
Nitric Oxide Pathway
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