Effects of hydrogen peroxide on the responsiveness of isolated canine bronchi: role of prostaglandin E2 and I2

1992 ◽  
Vol 263 (3) ◽  
pp. L402-L408 ◽  
Author(s):  
Y. Gao ◽  
P. M. Vanhoutte
Keyword(s):  
Hydrogen Peroxide ◽  
Methylene Blue ◽  
Smooth Muscle ◽  
Prostaglandin E2 ◽  
Respiratory Epithelium ◽  
Isometric Tension ◽  
Third Order ◽  
Bronchial Smooth Muscle ◽  
Cyclic Monophosphate

The present study was design to determine the role of prostaglandin E2 and I2 in the responses of isolated canine airways to H2O2. Rings of canine third-order bronchi, some of which had undergone mechanical denudation of the epithelium, were suspended in organ chambers; isometric tension was recorded. During contractions to acetylcholine, H2O2 induced concentration-dependent relaxations. The relaxations were attenuated significantly by indomethacin, acetylsalicylic acid, and methylene blue. H2O2 increased the release of prostaglandin E2 and 6-keto-prostaglandin F1 alpha and the content of adenosine 3',5'-cyclic monophosphate (cAMP). These effects were abolished by indomethacin or methylene blue. H2O2 did not affect the content of guanosine 3',5'-cyclic monophosphate significantly. These observations suggest that 1) H2O2 relaxes canine bronchial smooth muscle and 2) elevation of tissue content of cAMP induced by prostaglandin E2 and I2 may be involved. These phenomena did not appear to be modulated by the respiratory epithelium, since H2O2-induced relaxations and increases in the release of PGE2 and 6-ketoprostaglandin F1 alpha were similar in preparations with and without epithelium. However, after treatment with methylene blue, H2O2 induced contractions only in preparations with epithelium. These epithelium-dependent contractions were not affected by inhibitors of cyclooxygenase and lipoxygenase.

Epithelium acts as a modulator and a diffusion barrier in the responses of canine airway smooth muscle

1994 ◽  
Vol 76 (5) ◽  
pp. 1843-1847 ◽  
Author(s):  
Y. Gao ◽  
P. M. Vanhoutte
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Diffusion Barrier ◽  
Respiratory Epithelium ◽  
Isometric Tension ◽  
High Potassium

The present study was designed to determine the role of the respiratory epithelium as a diffusion barrier and a modulator of the responsiveness of airway smooth muscle to bronchoactive agents. Segments of canine bronchi, with or without epithelium, were suspended in organ chambers and perfused intraluminally. The isometric tension was recorded. Acetylcholine, given intraluminally, induced significantly smaller contractions in bronchi with than in bronchi without epithelium. When this agonist was given extraluminally, no difference in contractions was noted between the tissues. In the presence of acetylcholine and phentolamine, norepinephrine, given either intra- or extraluminally, induced significantly larger relaxations in bronchi with than in bronchi without epithelium. High potassium given intraluminally induced contractions only in bronchi without epithelium; however, in the presence of ouabain, both tissues contracted similarly. When high potassium was given extraluminally, no difference in contraction between tissues with and without epithelium was noted. When [3H]acetylcholine and [3H]norepinephrine were perfused intraluminally, the accumulation of 3H radioactivity in the extraluminal solutions was significantly less in bronchi with than in bronchi without epithelium. These observations suggest that the epithelium acts as both a diffusion barrier and a modulator of the responses of canine airways to bronchoactive agents.

Enhanced role of K+ channels in relaxations of hypercholesterolemic rabbit carotid artery to NO

1995 ◽  
Vol 269 (3) ◽  
pp. H805-H811 ◽  
Author(s):  
S. Najibi ◽  
R. A. Cohen
Keyword(s):  
Carotid Artery ◽  
Sodium Nitroprusside ◽  
Channel Blocker ◽  
Isometric Tension ◽  
K Channel ◽  
K Channels ◽  
Rabbit Carotid Artery ◽  
Cyclic Monophosphate ◽  
Endothelium Dependent Relaxation

Endothelium-dependent relaxations to acetylcholine remain normal in the carotid artery of hypercholesterolemic rabbits, but unlike endothelium-dependent relaxations of normal rabbits, they are inhibited by charybdotoxin, a specific blocker of Ca(2+)-dependent K+ channels. Because nitric oxide (NO) is the mediator of endothelium-dependent relaxation and can activate Ca(2+)-dependent K+ channels directly or via guanosine 3',5'-cyclic monophosphate, the present study investigated the role of Ca(2+)-dependent K+ channels in relaxations caused by NO, sodium nitroprusside, and 8-bromoguanosine 3',5'-cyclic monophosphate (8-Brc-GMP) in hypercholesterolemic rabbit carotid artery. Isometric tension was measured in rabbit carotid artery denuded of endothelium from normal and hypercholesterolemic rabbits which were fed 0.5% cholesterol for 12 wk. Under control conditions, relaxations to all agents were similar in normal and hypercholesterolemic rabbit arteries. Charybdotoxin had no significant effect on relaxations of normal arteries to NO, sodium nitroprusside, or 8-BrcGMP, but the Ca(2+)-dependent K+ channel blocker significantly inhibited the relaxations caused by each of these agents in the arteries from hypercholesterolemic rabbits. By contrast, relaxations to the calcium channel blocker nifedipine were potentiated to a similar extent by charybdotoxin in both groups. In addition, arteries from hypercholesterolemic rabbits relaxed less than normal to sodium nitroprusside when contracted with depolarizing potassium solution. These results indicate that although nitrovasodilator relaxations are normal in the hypercholesterolemic rabbit carotid artery, they are mediated differently, and to a greater extent, by Ca(2+)-dependent K+ channels. These data also suggest that K+ channel-independent mechanism(s) are impaired in hypercholesterolemia.

Levobupivacaine-induced contraction of isolated rat aorta is calcium dependent

2011 ◽  
Vol 89 (7) ◽  
pp. 467-476 ◽  
Author(s):  
Ji Seok Baik ◽  
Ju-Tae Sohn ◽  
Seong-Ho Ok ◽  
Jae-Gak Kim ◽  
Hui-Jin Sung ◽  
...  
Keyword(s):  
Methylene Blue ◽  
Smooth Muscle ◽  
Calcium Influx ◽  
Rat Aorta ◽  
Isometric Tension ◽  
Guanosine Monophosphate ◽  
Response Curves ◽  
Calcium Dependent ◽  
Isolated Rat

Levobupivacaine is a long-acting local anesthetic that intrinsically produces vasoconstriction in isolated vessels. The goals of this study were to investigate the calcium-dependent mechanism underlying levobupivacaine-induced contraction of isolated rat aorta in vitro and to elucidate the pathway responsible for the endothelium-dependent attenuation of levobupivacaine-induced contraction. Isolated rat aortic rings were suspended to record isometric tension. Cumulative levobupivacaine concentration–response curves were generated in either the presence or absence of the antagonists verapamil, nifedipine, SKF-96365, 2-aminoethoxydiphenylborate, Gd3+, NW-nitro-l-arginine methyl ester (L-NAME), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), and methylene blue, either alone or in combination. Verapamil, nifedipine, SKF-96365, 2-aminoethoxydiphenylborate, low calcium concentrations, and calcium-free Krebs solution attenuated levobupivacaine-induced contraction. Gd3+ had no effect on levobupivacaine-induced contraction. Levobupivacaine increased intracellular calcium levels in vascular smooth muscle cells. L-NAME, ODQ, and methylene blue increased levobupivacaine-induced contraction in endothelium-intact aorta. SKF-96365 attenuated calcium-induced contraction in a previously calcium-free isotonic depolarizing solution containing 100 mmol/L KCl. Levobupivacaine-induced contraction of rat aortic smooth muscle is mediated primarily by calcium influx from the extracellular space mainly via voltage-operated calcium channels and, in part, by inositol 1,4,5-trisphosphate receptor-mediated release of calcium from the sarcoplasmic reticulum. The nitric oxide – cyclic guanosine monophosphate pathway is involved in the endothelium-dependent attenuation of levobupivacaine-induced contraction.

Mechanisms of cyclic nucleotide-induced relaxation in canine tracheal smooth muscle

1995 ◽  
Vol 268 (3) ◽  
pp. L407-L413 ◽  
Author(s):  
I. McGrogan ◽  
S. Lu ◽  
S. Hipworth ◽  
L. Sormaz ◽  
R. Eng ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cyclic Nucleotide ◽  
Cyclopiazonic Acid ◽  
Inhibitory Effect ◽  
Beta Agonist ◽  
Cyclic Monophosphate ◽  
Median Effective Concentration ◽  
Camp Levels ◽  
Ca2 Channels

The effects of exogeneous cyclopiazonic acid (CPA, 10 microM), a selective inhibitor of the sarcoplasmic reticulum (SR) Ca2+ adenosinetriphosphatase, on cyclic nucleotide-induced relaxations of canine airway smooth muscle were examined. Strips of tracheal muscle were precontracted with carbachol (50% median effective concentration, 0.1 microM) or with 60 mM KCl. The beta-agonist isoproterenol (ISO, 10 microM) relaxed the tissue by approximately 50%. The relaxation was reduced in the presence of CPA when L-type Ca2+ channels were available but not when these were blocked by 0.1 microM nifedipine. Forskolin (1.0 microM), an adenylate cyclase activator, was less effective at inhibiting the contraction than ISO, and addition of CPA did not block its inhibitory effect as effectively as when ISO was used. Radioimmunoassay indicated that both these agents raised adenosine 3',5'-cyclic monophosphate (cAMP) levels to the same degree. Very little relaxation of the precontracted smooth muscle was elicited by 3 mM 8-bromo-adenosine 3',5'-cyclic monophosphate (8-BrcAMP), and addition of CPA had no effect. Sodium nitroprusside (100 microM) and 8-bromo-guanosine 3',5'-cyclic monophosphate (10 mM) inhibited contraction to a greater degree than any agent that raised cAMP. These inhibitions were greatly reduced in the presence of CPA when L-type Ca2+ channels were available. We conclude that pumping of Ca2+ into SR plays a major role guanosine 3',5'-cyclic monophosphate-produced but not cAMP-induced relaxation; L-type Ca2+ channels must be available for the relaxant role of Ca2+ pumping into the SR to be expressed; and ISO-induced relaxation may not involve primarily elevation of the cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

Melatonin potentiates contractile responses to serotonin in isolated porcine coronary arteries

2001 ◽  
Vol 280 (1) ◽  
pp. H76-H82 ◽  
Author(s):  
Qiong Yang ◽  
Elizabeth Scalbert ◽  
Philippe Delagrange ◽  
Paul M. Vanhoutte ◽  
Stephen T. O'Rourke
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Smooth Muscle ◽  
Coronary Arteries ◽  
Isometric Tension ◽  
Maximal Response ◽  
Melatonin Receptor ◽  
Vasomotor Tone ◽  
Vasoconstrictor Response ◽  
Coronary Vasomotor Tone

The present study was designed to determine the effects of melatonin on coronary vasomotor tone. Porcine coronary arteries were suspended in organ chambers for isometric tension recording. Melatonin (10−10-10−5 M) itself caused neither contraction nor relaxation of the tissues. Serotonin (10−9-10−5 M) caused concentration-dependent contractions of coronary arteries, and in the presence of melatonin (10−7 M) the maximal response to serotonin was increased in rings with but not without endothelium. In contrast, melatonin had no effect on contractions produced by the thromboxane A2 analog U-46619 (10−10-10−7 M). The melatonin-receptor antagonist S-20928 (10−6 M) abolished the potentiating effect of melatonin on serotonin-induced contractions in endothelium-intact coronary arteries, as did treatment with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10−5 M), methylene blue (10−5 M), or NG -nitro-l-arginine (3 × 10−5 M). In tissues contracted with U-46619, serotonin caused endothelium-dependent relaxations that were inhibited by melatonin (10−7 M). Melatonin also inhibited coronary artery relaxation induced by sodium nitroprusside (10−9-10−5 M) but not by isoproterenol (10−9-10−5 M). These results support the hypothesis that melatonin, by inhibiting the action of nitric oxide on coronary vascular smooth muscle, selectively potentiates the vasoconstrictor response to serotonin in coronary arteries with endothelium.

Rhythmic smooth muscle activity in hamster aortas is mediated by continuous release of NO from the endothelium

1991 ◽  
Vol 260 (1) ◽  
pp. H248-H253 ◽  
Author(s):  
W. F. Jackson ◽  
A. Mulsch ◽  
R. Busse
Keyword(s):  
Smooth Muscle ◽  
Soluble Guanylate Cyclase ◽  
Isometric Tension ◽  
Mechanical Activity ◽  
Continuous Release ◽  
Mechanical Removal ◽  
Camp Analogue ◽  
Rhythmic Contractions ◽  
Beta Adrenergic Agonist

Hamster aortas display endothelium-dependent, agonist-induced rhythmic contractions. However, the mechanism responsible for these oscillations is not known. Therefore, we investigated the possible role of nitric oxide (NO) on phenylephrine-induced rhythmicity in rings and segments of thoracic aortas of the hamster. We found that hamster aortas release NO, as detected by activation of purified soluble guanylate cyclase. The release of NO was abolished by mechanical removal of the endothelium or by exposure of the vessels to NG-nitro-L-arginine (NAG), a stereospecific selective inhibitor of NO synthesis. Correlated with the tonic release of NO was an elevation in guanosine 3',5'-cyclic monophosphate (cGMP) content in the vessels that could also be abolished by removal of the endothelium or treatment with NAG. The same procedures inhibited phenylephrine-induced isometric tension or diameter oscillations. Rhythmicity could be restored by exposure to the nitrovasodilator sodium nitroprusside, which increased cGMP levels in the aortas, or by exposure to the permeant analogue of cGMP, 8-BrcGMP. The beta-adrenergic agonist isoproterenol, as well as the cAMP analogue dibutyryl cAMP, failed to produce rhythmic contractions in either preparation. These data indicate that endothelium-derived NO, which stimulates the production of cGMP in the vascular smooth muscle, is the signal that leads to the observed rhythmic oscillations in smooth muscle mechanical activity.

Changes in cytosolic cGMP and calcium in airway smooth muscle relaxed by 3-morpholinosydnonimine

1994 ◽  
Vol 266 (1) ◽  
pp. L9-L16 ◽  
Author(s):  
K. A. Jones ◽  
R. R. Lorenz ◽  
D. O. Warner ◽  
Z. S. Katusic ◽  
G. C. Sieck
Keyword(s):  
Methylene Blue ◽  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Calcium Concentration ◽  
Cytosolic Calcium ◽  
Tracheal Smooth Muscle ◽  
Relative Importance ◽  
Cytosolic Calcium Concentration ◽  
Fura 2 ◽  
Cyclic Monophosphate

Nitrovasodilators relax airway smooth muscle by both guanosine 3',5'-cyclic monophosphate (cGMP)-dependent and cGMP-independent mechanisms and by mechanisms that reduce cytosolic calcium concentration ([Ca2+]i). This study was conducted to determine the relative importance of these mechanisms in relaxation of canine tracheal smooth muscle (CTSM) induced by 3-morpholinosydnonimine (SIN-1). We measured 1) the effect of SIN-1 on force, [cGMP]i, and [Ca2+]i, and 2) the ability of methylene blue (MB) to antagonize SIN-1-induced relaxation and cGMP accumulation. The ratio of fura 2 emission fluorescence intensities due to excitation at 340- and 380-nm wavelengths (F340/F380) was used as an index of [Ca2+]i. In strips contracted with 0.3 microM acetylcholine (ACh, n = 8) or 24 mM KCl (n = 8), SIN-1 (1-100 microM) caused a concentration-dependent decrease in force which was correlated with a concentration-dependent increase in [cGMP]i. MB (10 microM) proportionally attenuated both relaxation and cGMP accumulation. In fura 2-loaded strips contracted with 0.3 microM ACh (n = 7) or 30 mM KCl (n = 7), reductions in force induced by SIN-1 (1-100 microM) were accompanied by decreases in F340/F380. These findings suggest that in CTSM contracted with ACh or KCl, SIN-1 causes relaxation which appears to be mediated by cGMP-dependent mechanisms that reduce [Ca2+]i.

Physiological and pharmacological response of canine bronchial smooth muscle in situ

1983 ◽  
Vol 54 (1) ◽  
pp. 215-224 ◽  
Author(s):  
S. G. Hendrix ◽  
N. M. Munoz ◽  
A. R. Leff
Keyword(s):  
Smooth Muscle ◽  
Electrical Stimulation ◽  
Maximal Response ◽  
Repeated Injection ◽  
Third Order ◽  
Bronchial Smooth Muscle ◽  
Pure Nitrogen ◽  
Parasympathetic Ganglion ◽  
The Right

We studied the isometric response of bronchial smooth muscle in a single third-order bronchus of 24 dogs in situ. Length-tension studies were performed in six dogs by repeated injection of 10(-5) mol acetylcholine (ACh) into the right bronchoesophageal artery, and the resting tension (30.6 +/- 6.9 g/cm) and length (0.76 +/- 0.14 cm) permitting maximal contraction were determined. In eight other dogs, dose-related bronchial contraction was obtained with 10(-10) to 10(-5) mol intra-arterial (ia) ACh. Supramaximal electrical stimulation of the right cervical vagus nerve and bronchial parasympathetic ganglion stimulation with ia 1–1-dimethyl-4-phenylpiperazinium (DMPP) also caused bronchial contraction. The maximal response to ia ACh (28.5 +/- 1.7 g/cm), supramaximal electrical stimulation (15.2 +/- 1.1 g/cm), and ia DMPP (10.5 +/- 3.0 g/cm) was blocked by an ia dose of atropine (1–5 micrograms/kg) that did not alter the sympathetic relaxation response in the trachea. In four dogs, the bronchial response to sympathetic activation was studied by intravenous (iv) bolus injection of DMPP after cholinergic blockade with atropine. DMPP (25 micrograms/kg iv) caused 9.5 +/- 2.2 g/cm bronchial relaxation, which was blocked completely by 2–4 mg/kg iv propranolol. In six other dogs, hypoxia induced by ventilation with pure nitrogen caused bronchial contraction, which was blocked by vagotomy, atropine, and hexamethonium. We report a sensitive method for selective measurement of bronchial smooth muscle response in a single resistance bronchus. This preparation preserves regional innervation and circulation and permits selective physiological stimulation in situ.

Effects of cAMP on serotonin evoked calcium transients in cultured rat airway smooth muscle cells

1997 ◽  
Vol 272 (5) ◽  
pp. L865-L871 ◽  
Author(s):  
B. Tolloczko ◽  
Y. L. Jia ◽  
J. G. Martin
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Airway Smooth Muscle ◽  
Airway Smooth Muscle Cells ◽  
Intracellular Camp ◽  
Dependent Protein Kinase ◽  
Cyclic Monophosphate ◽  
Dependent Protein ◽  
High Concentrations

Agents increasing intracellular adenosine 3',5'-cyclic monophosphate (cAMP) cause relaxation of airway smooth muscle. However, the mechanisms of their action are not fully understood. We investigated the role of cAMP in the modulation of intracellular Ca2+ concentration ([Ca2+]i) transients evoked by serotonin (5-HT) in cultured rat tracheal smooth muscle (TSM) cells. Forskolin (10(-7) M) caused a significant elevation of intracellular cAMP and a 60% relaxation of tracheal rings contracted with 5-HT but did not affect [Ca2+]i in TSM cells. Forskolin (10(-5) M) completely relaxed tracheal rings and significantly decreased [Ca2+]i during the sustained phase of the 5-HT response. Forskolin-induced relaxation was attenuated by the cAMP-dependent protein kinase A (PKA) inhibitor Rp diastereomer of cAMP (Rp-cAMPS; 10(-4) M) and by the guanosine 3',5'-cyclic monophosphate (cGMP)-dependent protein kinase (PKG) inhibitor [Rp isomer of 8-(4-chlorophenylthio)-guanosine 3',5'-cyclic monophosphorothioate, 10(-4) M]. The effects of forskolin on [Ca2+]i were not altered by the PKA inhibitor but were abolished by the PKG inhibitor and thapsigargin. These results indicate that, in rat TSM, the relaxant effects of high concentrations of cAMP may be mediated, at least in part, by facilitating the sequestration of Ca2+ into intracellular stores by a mechanism involving PKG.

Interactions between nitroglycerin and endothelium in vascular smooth muscle relaxation

1991 ◽  
Vol 260 (3) ◽  
pp. H698-H701 ◽  
Author(s):  
J. L. Dinerman ◽  
D. L. Lawson ◽  
J. L. Mehta
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Muscle Relaxation ◽  
Smooth Muscle Relaxation ◽  
No Production ◽  
Cyclic Monophosphate ◽  
The Mean ◽  
Smooth Muscle Relaxant ◽  
Vascular Smooth Muscle Relaxation

To evaluate the role of endothelium in nitroglycerin (NTG)-mediated vascular relaxation, epinephrine-contracted rat thoracic aortic segments with and without intact endothelium were exposed to NTG (10(-10) to 10(-5) M). Aortic segments with intact (endo+, n = 15) and denuded endothelium (endo-, n = 9) exhibited typical NTG-induced relaxation. However, the mean effective concentration of NTG was lower for endo- than for endo+ segments (P less than 0.001). To determine if this phenomenon related to nitric oxide (NO) generation by endothelium, six endo+ segments were treated with NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO production. These endo+ segments exhibited greater (P less than 0.001) relaxation in response to NTG than the untreated endo+ segments. Oxyhemoglobin, an inhibitor of guanylate cyclase activation, greatly diminished NTG-mediated relaxation of all aortic segments. To determine if the enhanced NTG-mediated relaxation of endo- segments was unique to the guanosine 3',5'-cyclic monophosphate-dependent vasodilator NTG, other endo+ and endo- segments were exposed to adenosine 3',5'-cyclic monophosphate-dependent vasodilator papaverine (10(-8) to 10(-4) M), and no difference in EC50 was noted between endo+ and endo- segments. Thus endothelium attenuates NTG-mediated vasorelaxation, and this attenuation is abolished by inhibition of endothelial NO production with L-NMMA. These observations indicate that endothelium is a dynamic modulator of vascular smooth muscle relaxant effects of NTG. This modulation appears to result from a competitive interaction between endothelial NO and NTG.

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