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.

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.

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.

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.

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 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 Endothelial Nitric Oxide Synthase in Hypoxia-Induced Pial Artery Dilation

1998 ◽  
Vol 18 (5) ◽  
pp. 531-538 ◽  
Author(s):  
Michael J. Wilderman ◽  
William M. Armstead
Keyword(s):  
Nitric Oxide ◽  
No Synthase ◽  
Methionine Enkephalin ◽  
Cranial Window ◽  
Pial Artery ◽  
Endothelial No Synthase ◽  
Before And After ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Nitric oxide (NO) contributes to hypoxia-induced pial artery dilation, at least in part, through the formation of cGMP and the subsequent release of methionine enkephalin and leucine enkephalin in the newborn pig. In separate studies, these opioids also were observed to elicit NO-dependent pial artery dilation, whereas light/dye endothelial injury reduced hypoxic pial dilation. The current study was designed to investigate the role of the endothelial isoform of NO synthase in hypoxic pial dilation, associated opioid release, and opioid dilation in piglets equipped with a closed cranial window. N-iminoethyl-l-ornithine (l-NIO) (10−6 mol/L), an antagonist that may have greater endothelial NO synthase inhibitory selectivity, had no effect on dilation elicited by hypoxia (Po2 ≈ 35 mm Hg) (24 ± 2 versus 24 ± 2% in the absence and presence of l-NIO, respectively, n = 8). Hypoxic dilation was accompanied by increased CSF cGMP, which also was unchanged in the presence of l-NIO (394 ± 19 and 776 ± 63 versus 323 ± 13 and 739 ± 25 fmol/mL for control and hypoxia in the absence and presence of l-NIO, respectively, n = 6). Additionally, hypoxic pial dilation was associated with increased CSF methionine enkephalin, which also was unchanged in the presence of l-NIO (992 ± 73 and 2469 ± 197 versus 984 ± 18 and 2275 ± 185 pg/mL, respectively, n = 6). In contrast, methionine enkephalin–induced dilation was blocked by l-NIO (6 ± 1, 10 ± 1, and 16 ± 1 versus 1 ± 1, 1 ± 1, and 2 ± 1% for 10−10, 10−8, 10−6 mol/L methionine enkephalin, respectively, before and after l-NIO, n = 8). Substance P–induced pial dilation was blunted by l-NIO, whereas responses to sodium nitroprusside and N-methyl-d-aspartate were unchanged. These data indicate that endothelial NO synthase contributes to opioid-induced pial artery dilation but not hypoxia-induced dilation. Additionally, these data suggest that neuronally derived NO contributes to hypoxic pial dilation.

Nitric oxide-endothelin-1 interactions after surgically induced acute increases in pulmonary blood flow in intact lambs

2006 ◽  
Vol 290 (5) ◽  
pp. H1922-H1932 ◽  
Author(s):  
Peter Oishi ◽  
Anthony Azakie ◽  
Cynthia Harmon ◽  
Robert K. Fitzgerald ◽  
Albert Grobe ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Vascular Graft ◽  
Pulmonary Blood Flow ◽  
Heart Defects ◽  
No Synthase ◽  
Before And After ◽  
Nos Inhibitor ◽  
Surgically Induced

Several congenital heart defects require surgery that acutely increases pulmonary blood flow (PBF). This can lead to dynamic alterations in postoperative pulmonary vascular resistance (PVR) and can contribute to morbidity and mortality. Thus the objective of this study was to determine the role of nitric oxide (NO), endothelin (ET)-1, and their interactions in the alterations of PVR after surgically induced increases in PBF. Twenty lambs underwent placement of an aortopulmonary vascular graft. Lambs were instrumented to measure vascular pressures and PBF and studied for 4 h. Before and after shunt opening, lambs received an infusion of saline ( n = 9), tezosentan, an ETA- and ETB-receptor antagonist ( n = 6), or Nω-nitro-l-arginine (l-NNA), a NO synthase (NOS) inhibitor ( n = 5). In control lambs, shunt opening increased PBF by 117.8% and decreased PVR by 40.7% ( P < 0.05) by 15 min, without further changes thereafter. Plasma ET-1 levels increased 17.6% ( P < 0.05), and total NOS activity decreased 61.1% ( P < 0.05) at 4 h. ET-receptor blockade (tezosentan) prevented the plateau of PBF and PVR, such that PBF was increased and PVR was decreased compared with controls at 3 and 4 h ( P < 0.05). These changes were associated with an increase in total NOS activity (+61.4%; P < 0.05) at 4 h. NOS inhibition (l-NNA) after shunt placement prevented the sustained decrease in PVR seen in control lambs. In these lambs, PVR decreased by 15 min ( P < 0.05) but returned to baseline by 2 h. Together, these data suggest that surgically induced increases in PBF are limited by vasoconstriction, at least in part by an ET-receptor-mediated decrease in lung NOS activity. Thus NO appears to be important in maintaining a reduction in PVR after acutely increased PBF.

The role of nitric oxide in the baroreceptor-cardiac reflex in conscious Wistar rats

1995 ◽  
Vol 269 (3) ◽  
pp. H851-H855 ◽  
Author(s):  
N. Minami ◽  
Y. Imai ◽  
J. Hashimoto ◽  
K. Abe
Keyword(s):  
Nitric Oxide ◽  
Wistar Rats ◽  
Gain Control ◽  
No Synthase ◽  
Heart Period ◽  
Baroreflex Function ◽  
Before And After ◽  
Sigmoid Curve ◽  
Synthase Inhibitor

The role of nitric oxide (NO) in baroreceptor-cardiac reflex function was examined using a NO synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME), in conscious Wistar rats. Mean arterial pressure (MAP) and heart period (HP) relationships were obtained by intravenous injection of graded doses of phenylephrine and sodium nitroprusside (SNP). The baroreflex function was compared before and after L-NAME (10 mg/kg iv), L-NAME (10 mg/kg iv) followed by exogenous NO supplied as SNP (10-20 micrograms.kg-1.min-1 iv), or SNP alone (20 micrograms.kg-1.min-1 iv). To find the effect of changing basal MAP on baroreflex function, the baroreflex function was also examined before and after phenylephrine (8 micrograms.kg-1.min-1 iv) or L-NAME followed by concomitant infusion of SNP and phenylephrine. L-NAME increased basal MAP as well as HP from 104 +/- 1 to 141 +/- 2 mmHg and from 168 +/- 3 to 237 +/- 7 ms, respectively. L-NAME shifted the sigmoid curve in the direction of higher MAP with a significant increase in the gain (gain: control 2.14 +/- 0.15 ms/mmHg, L-NAME 3.70 +/- 0.26 ms/mmHg, P < 0.001). L-NAME together with SNP infusion did not significantly affect the gain, basal MAP, or HP. Infusion of SNP alone shifted the sigmoid curve in the direction of lower MAP but had no significant effect on the gain. An infusion of phenylephrine or L-NAME with concomitant infusion of SNP and phenylephrine increased basal MAP similarly as L-NAME alone did but had no significant effect on the gain.(ABSTRACT TRUNCATED AT 250 WORDS)

Endogenous nitric oxide and allergic bronchial hyperresponsiveness in guinea pigs

1997 ◽  
Vol 273 (3) ◽  
pp. L656-L662 ◽  
Author(s):  
S. Mehta ◽  
J. M. Drazen ◽  
C. M. Lilly
Keyword(s):  
Nitric Oxide ◽  
Guinea Pigs ◽  
Bronchial Hyperresponsiveness ◽  
No Synthase ◽  
Similar Degree ◽  
Endogenous Nitric Oxide ◽  
Expired Gas ◽  
Airway Tone ◽  
Bronchodilator Activity

To address the role of endogenous pulmonary nitric oxide (NO) in the modulation of airway tone, we investigated changes in expired NO levels, measured by chemiluminescence, and the effect of inhibition of NO synthase on inflammation-associated bronchial hyperresponsiveness in guinea pigs. Mixed expired gas NO levels were similar at baseline in antigen-exposed and unexposed animals and increased transiently to a similar degree during histamine-induced bronchoconstriction in both groups of animals [155 +/- 12% (15 +/- 1 to 23 +/- 4 ppb, P < 0.01) and 162 +/- 19% (16 +/- 2 to 25 +/- 3 ppb, P < 0.01) of baseline, respectively, after administration of 30 nmol/kg histamine]. Although inhibition of NO synthase with intravenous NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg) enhanced bronchial responsiveness to histamine by 30 +/- 8% in unexposed animals (P < 0.05), L-NAME did not enhance histamine responsiveness in antigen-exposed animals exhibiting bronchial hyperresponsiveness 24 h after antigen exposure. Thus bronchial hyperresponsiveness induced by repeated pulmonary antigen exposure may be associated with a transient defect in NO-related homeostatic bronchodilator activity.

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