Propofol Potentiates Phenylephrine-induced Contraction via  Cyclooxygenase Inhibition in Pulmonary Artery Smooth Muscle

2001 ◽  
Vol 94 (5) ◽  
pp. 833-839 ◽  
Author(s):  
Koji Ogawa ◽  
Satoru Tanaka ◽  
Paul A. Murray
Keyword(s):  
Arachidonic Acid ◽  
Smooth Muscle ◽  
In Vitro Study ◽  
Isometric Tension ◽  
Relaxation Response ◽  
Response Curves ◽  
Independent Manner ◽  
Pulmonary Arterial

Background The authors previously demonstrated in vivo that the pulmonary vasoconstrictor response to the a agonist phenylephrine is potentiated during propofol anesthesia compared with the conscious state. The current in vitro study tested the hypothesis that propofol potentiates phenylephrine-induced contraction by inhibiting the synthesis and/or activity of vasodilator metabolites of the cyclooxygenase pathway. Methods Canine pulmonary arterial rings were suspended for isometric tension recording. Intracellular calcium concentration ([Ca2+]i) was measured in pulmonary arterial strips loaded with acetoxylmethyl ester of fura-2. After phenylephrine-induced contraction, propofol (10(-7) to 10(-4) M) was administered in the presence or absence of the cyclooxygenase inhibitor ibuprofen (10(-5) M). The effects of propofol on the arachidonic acid and prostacyclin relaxation-response curves were assessed. The amount of 6-keto prostaglandin F1alpha (stable metabolite of prostacyclin) released from pulmonary vascular smooth muscle in response to phenylephrine was measured with enzyme immunoassay in the presence or absence of propofol and ibuprofen. Results Propofol potentiated phenylephrine-induced contraction in pulmonary arterial rings in a concentration-dependent and endothelium-independent manner. In endothelium-denuded strips, propofol (10(-4) M) increased tension by 53+/-11%, and increased [Ca2+]i by 56+/-9%. Ibuprofen also potentiated phenylephrine-induced contraction but abolished the propofol-induced increases in tension and [Ca2+]i. Propofol had no effect on the relaxation response to prostacyclin, whereas propofol and ibuprofen attenuated the relaxation response to arachidonic acid to a similar extent. Phenylephrine markedly increased 6-keto prostaglandin F1alpha production, and this effect was virtually abolished by propofol and ibuprofen. Conclusion These results suggest that propofol potentiates alpha-adrenoreceptor-mediated pulmonary vasoconstriction by inhibiting the concomitant production of prostacyclin by cyclooxygenase.

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.

Histamine tachyphylaxis in canine airways despite prostaglandin synthesis inhibition

1988 ◽  
Vol 65 (5) ◽  
pp. 1944-1949 ◽  
Author(s):  
P. J. Antol ◽  
S. J. Gunst ◽  
R. E. Hyatt
Keyword(s):  
Smooth Muscle ◽  
Dose Response ◽  
Prostaglandin Synthesis ◽  
Response Curves ◽  
Synthesis Inhibition ◽  
High Concentrations ◽  
Alpha Chloralose ◽  
Prostaglandin Synthesis Inhibitors

Tachyphylaxis to aerosolized histamine was studied in dogs anesthetized with thiamylal after pretreatment with prostaglandin synthesis inhibitors. Three consecutive histamine dose-response curves were obtained in nine dogs pretreated with 5 mg/kg indomethacin; two of these nine were also pretreated with 10 mg/kg indomethacin. Seven of the nine dogs were pretreated with 4 mg/kg sodium meclofenamate; four of these seven were also pretreated with 12 mg/kg. All dogs had tachyphylaxis at high concentrations of histamine regardless of inhibitor used. Pretreatment with indomethacin while the dogs were under alpha-chloralose-urethan anesthesia gave similar results. Histamine tachyphylaxis was also studied both in the presence and in the absence of indomethacin in tracheal smooth muscle strips obtained from seven additional dogs. A decrease in the median effective dose to histamine was observed in the indomethacin-treated strips, but tachyphylaxis to histamine remained. We conclude that prostaglandin synthesis inhibition does not reverse histamine tachyphylaxis either in vivo or in vitro. Thus the mechanism of histamine tachyphylaxis remains unexplained.

scholarly journals LncRNA-SMILR modulates RhoA/ROCK signaling by targeting miR-141 to regulate vascular remodeling in pulmonary arterial hypertension

2020 ◽  
Vol 319 (2) ◽  
pp. H377-H391 ◽  
Author(s):  
Si Lei ◽  
Fei Peng ◽  
Mei-Lei Li ◽  
Wen-Bing Duan ◽  
Cai-Qin Peng ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Long Noncoding Rna ◽  
Vascular Remodeling ◽  
Noncoding Rna ◽  
In Vivo Models ◽  
Pulmonary Arterial

Smooth muscle-enriched long noncoding RNA (SMILR), as a long noncoding RNA (lncRNA), was increased in pulmonary arterial hypertension (PAH) patients and in vitro and in vivo models. SMILR activated RhoA/ROCK signaling by targeting miR-141 to disinhibit its downstream target RhoA. SMILR knockdown or miR-141 overexpression inhibited hypoxia-induced cell proliferation and migration via repressing RhoA/ROCK signaling in pulmonary arterial smooth muscle cells (PASMCs), which was confirmed in vivo experiments that knockdown of SMILR inhibited vascular remodeling and alleviated PAH in rats. SMILR may be a promising and novel therapeutic target for the treatment and drug development of PAH.

Sex Difference In Platelet Response To Aspirin Treatment

1981 ◽  
Author(s):  
N S Nicholson ◽  
S L Smith ◽  
R N Saunders
Keyword(s):  
Arachidonic Acid ◽  
Sex Difference ◽  
In Vitro Study ◽  
Female Rats ◽  
Platelet Response ◽  
Male And Female Rats ◽  
Males And Females ◽  
Spontaneous Aggregation

This study was done to determine if a sex difference in response to aspirin similar to that seen in the clinic could be demonstrated in an animal model with hyperactive platelets. The platelet hyperactivity which results in the spontaneous formation of platelet aggregates in retired breeder rats was reduced in both male and female rats by sulfinpyrazone, dipyridamole and indomethacin administered at 20 mg/kg. Aspirin blocked spontaneous aggregation in the male, but had no effect in the female even at doses of 100 mg/kg. Because aspirin is known to be an inhibitor of cyclooxygenase, the metabolism of arachidonic acid was studied in these rats. Arachidonic acid at 20 mg/kg was active in reducing spontaneous aggregation in the male, but had no effect in the female. However, in an in vitro study of the metabolism of arachidonic acid, no significant differences were seen between males and females in the conversion of arachidonic acid to PGF2α, PGE2, TXB2 or HHT. Aspirin was equally effective in both males and females in blocking the in vitro conversion of arachidonic acid via the cyclooxygenase pathway. The retired breeder rat provides a system for meaningful investigations toward understanding the human sex-related differences in platelet sensitivity with aspirin, although the mechanisms of the in vivo male/female platelet sensitivity have not been explained by in vitro studies thus far.

Mepivacaine attenuates vasodilation induced by ATP-sensitive potassium channels in rat aorta

2016 ◽  
Vol 94 (11) ◽  
pp. 1211-1219 ◽  
Author(s):  
Jiseok Baik ◽  
Seong-Ho Ok ◽  
Eun-Jin Kim ◽  
Dawon Kang ◽  
Jeong-Min Hong ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Combined Treatment ◽  
In Vitro Study ◽  
Rat Aorta ◽  
Response Curves ◽  
Membrane Hyperpolarization ◽  
Pkc Inhibitor ◽  
Induced Membrane ◽  
Kinase C

The goal of this in vitro study was to investigate the effect of mepivacaine on vasodilation induced by the ATP-sensitive potassium (KATP) channel opener levcromakalim in isolated endothelium-denuded rat aortas. The effects of mepivacaine and the KATP channel inhibitor glibenclamide, alone or in combination, on levcromakalim-induced vasodilation were assessed in the isolated aortas. The effects of mepivacaine or combined treatment with a protein kinase C (PKC) inhibitor, GF109203X, and mepivacaine on this vasodilation were also investigated. Levcromakalim concentration–response curves were generated for isolated aortas precontracted with phenylephrine or a PKC activator, phorbol 12,13-dibutyrate (PDBu). Further, the effects of mepivacaine and glibenclamide on levcromakalim-induced hyperpolarization were assessed in rat aortic vascular smooth muscle cells. Mepivacaine attenuated levcromakalim-induced vasodilation, whereas it had no effect on this vasodilation in isolated aortas pretreated with glibenclamide. Combined treatment with GF109203X and mepivacaine enhanced levcromakalim-induced vasodilation compared with pretreatment with mepivacaine alone. This vasodilation was attenuated in aortas precontracted with PDBu compared with those precontracted with phenylephrine. Mepivacaine and glibenclamide, alone or in combination, attenuated levcromakalim-induced membrane hyperpolarization. Taken together, these results suggest that mepivacaine attenuates vasodilation induced by KATP channels, which appears to be partly mediated by PKC.

Modulation by Dipyridamole of the Arachidonic Acid Metabolic Pathway in Platelets an in vivo and in vitro Study

1979 ◽  
Author(s):  
Neri G.G. Serneri ◽  
G. F. Gensini ◽  
R. Abbate ◽  
S. Favilla ◽  
R. Laureano
Keyword(s):  
Arachidonic Acid ◽  
Antiplatelet Agent ◽  
In Vitro Study ◽  
Inhibitory Effect ◽  
Oral Route ◽  
Radiometric Assay ◽  
Venous Infusion ◽  
Clinical Conditions

Dipyridamole is a useful antiplatelet agent in specific clinical conditions, but its effects on TxEL production by platelets are now being debated, Resting platelets from patients with 1.5-2 fig/ml serum dipyridamole (spectrofluorimetric assay). administered by venous infusion or by oral route, showed an increased concentration (m.v. +60% P<0.001) of cAMP (radiometric assay). After stimulation with thrombin (5U/ml) platelets produced a significantly decreased amount of TxB(m.v. -60%, F< 0.001) (radioimmunoassay with antibody kindly supplied by Doctor J.B. Smith, Philadelphia). However also after stimulation with arachidonic acid (A.A.) 1 mM TxB production was decreased(m.v. -50%, P<0.001). The incubation of control platelets with different concentrations of dipyridamole (0.5, 1 and 2 μg/ml) for 20 min at 37°C resulted in an increase of cAMP and in a decrease of TxB, production after stimulation with thrombin and with A.A.. These results indicate that dipyridamole is endowed with direct antiaggrega= ting activity caused by a decreased production of TxB2. This in tum seems due to an inhibitory modulating effect of cAMP on arachidonic acid cyclo-oxygenation. However our findings do not rule out an inhibitory effect also on phospholipase A2.

In vitro reactivity of ventral aorta to acetylcholine and noradrenaline in yellow freshwater eel (Anguilla anguilla L.) acclimatized to 10.1 MPa hydrostatic pressure

2000 ◽  
Vol 78 (11) ◽  
pp. 897-903 ◽  
Author(s):  
François Guerrero ◽  
Mickael Theron ◽  
Philippe Sebert
Keyword(s):  
Smooth Muscle ◽  
Hydrostatic Pressure ◽  
Vascular Smooth Muscle ◽  
Dose Response ◽  
Vascular Reactivity ◽  
Anguilla Anguilla ◽  
Dry Weight ◽  
Isometric Tension ◽  
Response Curves

We examined in vitro vascular reactivity of eels previously acclimatized to 10.1 MPa hydrostatic pressure (HP) for 21 days. The isometric tension developed by ventral aortic rings was measured at atmospheric pressure. Dose-response curves for either acetylcholine (ACh) or noradrenaline (NA), as well as contractions evoked by 80 mM K+, were compared with time-matched experiments conducted on rings obtained from control eels. Results showed that neither the optimal tension nor the maximal force of the K+-evoked contraction were significantly modified, suggesting that acclimatization to high HP did not change the vascular smooth muscle contractile machinery. The dose-response curve to ACh was not significantly changed. Conversely, although NA always relaxed aortic rings, the response of acclimatized eels was significantly reduced over the entire range of the agonist concentration tested (10-8 to 10-3 M), except for the lowest one (10-9 M). The maximal amplitude of the NA-induced relaxation was significantly reduced in aortic rings from acclimatized eels as compared with non-acclimatized samples (339.3 ± 86.5 vs. 744.3 ± 72.1 mg·mg-1 dry weight, P < 0.005). Our results suggest that acclimatization to high HP could selectively alter the control of vascular tone by catecholamines.Key words: fish, high pressure, vascular smooth muscle, adrenoceptors, cholinergic receptors.

Antidiarrheal Activity of Ethanol Extract of Ophioglossum Vulgatum In Mice And Spasmolytic Effect on Smooth Muscle Contraction of Isolated Jejunum In Rabbits

2020 ◽  
Author(s):  
Jianwu Zhang ◽  
Lan Yang ◽  
Yingying Fang ◽  
Jing Li ◽  
Chunxia Gu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
High Performance ◽  
Chemical Constituents ◽  
Ethanol Extract ◽  
Gastrointestinal Diseases ◽  
Control Group ◽  
Response Curves ◽  
Antidiarrheal Activity

Abstract BackgroundOphioglossum vulgatum Linn. (Ophioglossaceae) (OV), which is traditionally used on wounds and burns, enjoys a reputation as the king of medicine in Taiwan. There are few studies on its role in gastrointestinal diseases. Our aim was to assess the antidiarrheal and spasmolytic effect of the ethanol whole plant extract of Ophioglossum vulgatum (EWOV).MethodsStudy was conducted from June 2018 to July 2019. The chemical constituents of EWOV were analyzed by high performance liquid chromatography (HPLC). In vivo, the antidiarrheal activity of EWOV (125, 250 and 500 mg/kg; orally) in castor oil-induced Kun Ming mice was evaluated. In vitro, the effect of EWOV (0.01-10 mg/mL) on the spontaneous contraction of isolated rabbit jejunum smooth muscle was studied. Verapamil was the positive control group in both vivo and vitro studies. The jejunum stripes were pre-contracted by ACh (10-5 M) and KCl (60 mM) which could induce the jejunum spasm. The possible spasmolytic effect was analyzed in the pretreatment of the jejunum preparations with EWOV (0.3, 1 mg/mL) or verapamil (0.03, 0.1 µM) in Ca2+-free and high-K+ (60 mM) solution containing EDTA.ResultsEWOV (250 and 500 mg/kg) exhibited antidiarrheal effect. EWOV (0.01-10 mg/mL) inhibited the spontaneous and ACh/KCl-induced contraction with an EC50 value of 1.46 (0.89-2.04), 1.06 (0.63-1.48) and 0.48 (0.29-0.67), and it shifted the concentration-response curves of CaCl2 to right with decreased in max, similar to verapamil. ConclusionsEWOV has significant antidiarrheal and spasmolytic effect, possibly by mediating calcium channel blocking activity, this provides the pharmacological basis for use in gastrointestinal disorders.

Neutral endopeptidase modulates neurotensin-induced airway contraction

1989 ◽  
Vol 66 (5) ◽  
pp. 2338-2343 ◽  
Author(s):  
T. D. Djokic ◽  
D. J. Dusser ◽  
D. B. Borson ◽  
J. A. Nadel
Keyword(s):  
Smooth Muscle ◽  
Serine Proteases ◽  
Neutral Endopeptidase ◽  
Smooth Muscle Contraction ◽  
Response Curves ◽  
Terminal Fragment ◽  
Carboxypeptidase N

To determine the role of endogenous neutral endopeptidase (NEP) (also called enkephalinase, EC 3.4.24.11) in regulating neurotensin-induced airway contraction, we used phosphoramidon, a specific NEP inhibitor, in the guinea pig. In studies in vitro, neurotensin and the COOH-terminal fragment neurotensin-(8–13) contracted strips of bronchial smooth muscle in a concentration-dependent fashion (P less than 0.001). In contrast, the NH2-terminal fragment neurotensin-(1–11) and the COOH-terminal fragment neurotensin-(12–13), the main fragments of neurotensin hydrolysis by NEP, had no effect. Phosphoramidon (10(-5) M) did not change resting tension but shifted the concentration-response curves to neurotensin to lower concentrations (P less than 0.001), whereas inhibitors of kininase II, aminopeptidases, serine proteases, and carboxypeptidase N were without effect. Removing the epithelium increased the contractile response to neurotensin (P less than 0.001), and phosphoramidon further increased the response to neurotensin in these tissues (P less than 0.001). Similar results were obtained in studies in vivo using aerosolized neurotensin and phosphoramidon. These results suggest that endogenous NEP in the airways modulates the effects of neurotensin on airway smooth muscle contraction by inactivating the peptide.

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