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.

Mepivacaine-induced contraction is attenuated by endothelial nitric oxide release in isolated rat aorta

2012 ◽  
Vol 90 (7) ◽  
pp. 863-872 ◽  
Author(s):  
Hui-Jin Sung ◽  
Mun-Jeoung Choi ◽  
Seong-Ho Ok ◽  
Soo Hee Lee ◽  
Il Jeong Hwang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Calcium Influx ◽  
Guanosine Monophosphate ◽  
Krebs Solution ◽  
High Concentration ◽  
Response Curves ◽  
Endothelial Nitric Oxide ◽  
Isolated Rat

Mepivacaine is an aminoamide-linked local anesthetic with an intermediate duration that intrinsically produces vasoconstriction both in vivo and in vitro. The aims of this in-vitro study were to examine the direct effect of mepivacaine in isolated rat aortic rings and to determine the associated cellular mechanism with a particular focus on endothelium-derived vasodilators, which modulate vascular tone. In the aortic rings with or without endothelium, cumulative mepivacaine concentration–response curves were generated in the presence or absence of the following antagonists: Nω-nitro-l-arginine methyl ester [l-NAME], indomethacin, fluconazole, methylene blue, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one [ODQ], verapamil, and calcium-free Krebs solution. Mepivacaine produced vasoconstriction at low concentrations (1 × 10−3 and 3 × 10−3 mol/L) followed by vasodilation at a high concentration (1 × 10−2 mol/L). The mepivacaine-induced contraction was higher in endothelium-denuded aortae than in endothelium-intact aortae. Pretreatment with l-NAME, ODQ, and methylene blue enhanced mepivacaine-induced contraction in the endothelium-intact rings, whereas fluconazole had no effect. Indomethacin slightly attenuated mepivacaine-induced contraction, whereas verapamil and calcium-free Krebs solution more strongly attenuated this contraction. The vasoconstriction induced by mepivacaine is attenuated mainly by the endothelial nitric oxide – cyclic guanosine monophosphate pathway. In addition, mepivacaine-induced contraction involves cyclooxygenase pathway activation and extracellular calcium influx via voltage-operated calcium channels.

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.

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.

Differential effects of nitrovasodilators and nitric oxide on porcine tracheal and bronchial muscle in vitro

1994 ◽  
Vol 77 (3) ◽  
pp. 1142-1147 ◽  
Author(s):  
K. Stuart-Smith ◽  
T. C. Bynoe ◽  
K. S. Lindeman ◽  
C. A. Hirshman
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Smooth Muscle ◽  
Sodium Nitroprusside ◽  
Airway Smooth Muscle ◽  
Muscle Relaxation ◽  
Ringer Solution ◽  
Smooth Muscle Relaxation ◽  
Response Curves

Nitrovasodilators and nitric oxide relax airway smooth muscle. The mechanism by which nitrovasodilators are thought to act is by release of nitric oxide, but the importance of nitric oxide in nitrovasodilator-induced airway smooth muscle relaxation is unclear. The aim of this study was to compare the relaxing effects of nitric oxide itself with those of nitrovasodilators in porcine tracheal muscle and intrapulmonary airways and to investigate the mechanisms involved. Strips of porcine tracheal smooth muscle, rings of bronchi, and strips of bronchi from the same animal were suspended in organ chambers in modified Krebs Ringer solution (95% O2–5% CO2, 37 degrees C). Tissues were contracted with carbachol, and concentration-response curves to nitric oxide, sodium nitroprusside, and SIN-1 (an active metabolite of molsidomine) were obtained. All tissues relaxed to sodium nitroprusside, SIN-1, and nitric oxide. The relaxation to nitric oxide but not to SIN-1 or sodium nitroprusside was inhibited by methylene blue. Tissues pretreated with methylene blue that failed to relax to nitric oxide were, however, relaxed by sodium nitroprusside. These results demonstrate that nitrovasodilators relax airways by a mechanism other than by or in addition to the release of nitric oxide.

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.

scholarly journals Effects of abnormal cannabidiol on oxytocin-induced myometrial contractility

Reproduction ◽  
2010 ◽  
Vol 139 (4) ◽  
pp. 783-788 ◽  
Author(s):  
Diarmaid D Houlihan ◽  
Michael C Dennedy ◽  
John J Morrison
Keyword(s):  
Methylene Blue ◽  
Guanylate Cyclase ◽  
Inhibitory Effect ◽  
Isometric Tension ◽  
Tissue Type ◽  
Elective Cesarean Section ◽  
Uterine Contractility ◽  
Response Curves ◽  
Myometrial Contractility

The objective of this study was to investigate the effects of abnormal cannabidiol (abn-cbd) on oxytocin-induced myometrial contractility occurring during pregnancy. Isometric tension recordings were performed in isolated myometrial strips from biopsies obtained at elective cesarean section. The effects of cumulative doses of abn-cbd (10−9–10−5 M) on oxytocin-induced myometrial contractions alone, and on those following pre-incubation with SR 144528, AM 251, methylene blue, and iberiotoxin were measured, and dose–response curves were constructed. The pD2(−log EC50) values and the maximal inhibitory (MMI) values that were achieved were compared for each tissue type. Abn-cbd exerted a potent relaxant effect on oxytocin-induced myometrial contractionsin vitro. Pre-incubation with the guanylate cyclase inhibitor, methylene blue, and the BKCachannel antagonist, iberiotoxin, significantly attenuated this effect (for pD2,P<0.01; for MMI,P<0.01). Abn-cbd exerts a potent inhibitory effect on human uterine contractility. This effect is partially mediated through modulation of guanylate cyclase and activation of BKCachannel activity. These findings have implications for physiologic regulation of myometrial quiescence.

Vasorelaxant Effect of Novel Nitric Oxide-Hydrogen Sulfide Donor Chalcone in Isolated Rat Aorta: Involvement of cGMP Mediated sGC and Potassium Channel Activation

2020 ◽  
Vol 13 (2) ◽  
pp. 126-136
Author(s):  
Amol Sherikar ◽  
Rakesh Dhavale ◽  
Manish Bhatia
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Hydrogen Sulfide ◽  
Potassium Channel ◽  
Rat Aorta ◽  
Tetraethylammonium Chloride ◽  
Vasorelaxant Effect ◽  
Activation Assay ◽  
Isolated Rat

Background and Objective: : Recently, nitric oxide (NO) and hydrogen sulfide (H2S) donating moieties were extensively studied for their role in the vasculature as they are responsible for many cellular and pathophysiological functioning. The objective of the present study is to evaluate novel NO and H2S donating chalcone moieties on isolated rat aorta for vasorelaxation, and to investigate the probable mechanism of action. Methods:: To extend our knowledge of vasorelaxation by NO and H2S donor drugs, here we investigated the vasorelaxing activity of novel NO and H2S donating chalcone moieties on isolated rat aorta. The mechanism of vasorelaxation by these molecules was investigated by performing in vitro cGMP mediated sGC activation assay and using Tetraethylammonium chloride (TEA) as a potassium channel blocker and Methylene blue as NO blocker. Results:: Both NO and H2S donating chalcone moieties were found to be potent vasorelaxant. The compound G4 and G5 produce the highest vasorelaxation with 3.716 and 3.789 M of pEC50, respectively. After the addition of TEA, G4 and G5 showed 2.772 and 2.796 M of pEC50, respectively. The compounds Ca1, Ca2, and D7 produced significant activation and release of cGMP mediated sGC which was 1.677, 1.769 and 1.768 M of pEC50, respectively. Conclusion: : The vasorelaxation by NO-donating chalcones was blocked by Methylene blue but it did not show any effect on H2S donating chalcones. The vasorelaxing potency of NO-donating molecules was observed to be less affected by the addition of TEA but H2S donors showed a decrease in both efficacy and potency. The cGMP release was more in the case of NO-donating molecules. The tested compounds were found potent for relaxing vasculature of rat aorta.

Effects of Halothane and Isoflurane on Carbon Monoxide-induced Relaxations in the Rat Aorta

1996 ◽  
Vol 85 (2) ◽  
pp. 347-354 ◽  
Author(s):  
Ming Jing ◽  
Saiid Bina ◽  
Ajay Verma ◽  
Jayne L. Hart ◽  
Sheila M. Muldoon
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Cyclic Guanosine Monophosphate ◽  
Rat Aorta ◽  
Isometric Tension ◽  
Guanosine Monophosphate ◽  
Second Procedure ◽  
Dose Dependent ◽  
Cgmp Formation ◽  
Isolated Rat

Background Halothane and isoflurane previously were reported to attenuate endothelium-derived relaxing factor/nitric oxide-mediated vasodilation and cyclic guanosine monophosphate (cGMP) formation in isolated rat aortic rings. Carbon monoxide has many chemical and physiologic similarities to nitric oxide. This study was designed to investigate the effects of halothane and isoflurane on carbon monoxide-induced relaxations and cGMP formation in the isolated rat aorta. Methods Isometric tension was recorded continuously from endothelium denuded rat aortic rings suspended in Krebs-filled organ baths. Rings precontracted with submaximal concentrations of norepinephrine were exposed to cumulative concentrations of carbon monoxide (26-176 microM). This procedure was repeated three times, with anesthetics delivered 10 min before the second procedure. Carbon monoxide responses of rings contracted with the same concentration of norepinephrine (10(-6) M and 2 x 10(-6) M) used in the anesthetic-exposed preparations also were examined. The concentrations of cGMP were determined in denuded rings using radioimmunoassay. The rings were treated with carbon monoxide (176 microM, 30 s) alone, or carbon monoxide after a 10-min incubation with halothane (0.34 mM or 0.72 mM). To determine whether the sequence of anesthetic delivery influenced results, vascular rings pretreated with halothane were compared with nonpretreated rings. Results Carbon monoxide (26-176 microM) caused a dose-dependent reduction of norepinephrine-induced tension, with a maximal relaxation of 1.51 +/- 0.07 g (85 +/- 7% of norepinephrine-induced contraction). Halothane (0.34 mM and 0.72 mM) significantly attenuated the carbon monoxide-induced relaxations, but only the highest concentration of isoflurane (0.53 mM) significantly attenuated the carbon monoxide-induced relaxations. Carbon monoxide (176 microM) significantly increased cGMP content (+88.1 +/- 7.1%) and preincubation of the aortic rings with halothane (0.34 mM and 0.72 mM) inhibited this increase (-70.7 +/- 6.8% and -108.1 +/- 10.6%, respectively). When aortic rings and carbon monoxide were added simultaneously to Krebs solution equilibrated with halothane (0.72 mM), no inhibition of cGMP formation occurred. Conclusion Carbon monoxide-induced endothelium-independent relaxations of rat aortic rings were decreased by clinically relevant concentrations of halothane and isoflurane. The carbon monoxide-induced elevations of cGMP were attenuated by halothane only when the anesthetic was incubated with aortic rings before carbon monoxide treatment. The possible clinical significance of the actions of the anesthetics on this endogenous vasodilator is yet to be determined.

Calcium sensitization involved in dexmedetomidine-induced contraction of isolated rat aorta

2011 ◽  
Vol 89 (9) ◽  
pp. 681-689 ◽  
Author(s):  
Jae-Gak Kim ◽  
Hui-Jin Sung ◽  
Seong-Ho Ok ◽  
Seong-Chun Kwon ◽  
Kwang Seong Cheon ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Rho Kinase ◽  
In Vitro Study ◽  
High Dose ◽  
Membrane Translocation ◽  
Response Curves ◽  
Aortic Smooth Muscle ◽  
Gf 109203X ◽  
Isolated Rat

Dexmedetomidine, a full agonist of the α2B-adrenoceptor that is mainly involved in vascular smooth muscle contraction, is primarily used for analgesia and sedation in intensive care units. High-dose dexmedetomidine produces hypertension in children and adults. The goal of this in vitro study was to investigate the role of the calcium (Ca2+) sensitization mechanism involving Rho-kinase, protein kinase C (PKC), and phosphoinositide 3-kinase (PI3-K) in mediating contraction of isolated rat aortic smooth muscle in response to dexmedetomidine. The effect of dexmedetomidine on the intracellular Ca2+ level ([Ca2+]i) and tension was measured simultaneously. Dexmedetomidine concentration–response curves were generated in the presence or absence of the following antagonists: rauwolscine, Y 27632, LY 294002, GF 109203X, and verapamil. Dexmedetomidine-induced phosphorylation of PKC and membrane translocation of Rho-kinase were detected with Western blotting. Rauwolscine, Y 27632, GF 109203X, LY 294002, and verapamil attenuated dexmedetomidine-induced contraction. The slope of the [Ca2+]i–tension curve for dexmedetomidine was higher than that for KCl. Dexmedetomidine induced phosphorylation of PKC and membrane translocation of Rho-kinase. These results suggest that dexmedetomidine-induced contraction involves a Ca2+ sensitization mechanism mediated by Rho-kinase, PKC, and PI3-K that is secondary to α2-adrenoceptor stimulation in rat aortic smooth muscle.

The basal endothelial inhibitory influence on vascular tone is not affected in nitroglycerin-tolerant rat aorta

1994 ◽  
Vol 72 (9) ◽  
pp. 1094-1097 ◽  
Author(s):  
J. Van de Voorde ◽  
S. Vyt ◽  
B. Vanheel
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Smooth Muscle ◽  
Vascular Tone ◽  
Prolonged Exposure ◽  
Rat Aorta ◽  
Nitrate Tolerance ◽  
Inhibitory Influence ◽  
And Control

Prolonged exposure to nitrovasodilators produces tolerance and dependence. Nitrovasodilators exert their action on vascular smooth muscle cells by activation of guanylyl cyclase. Nitrates share this mechanism with endothelial NO, which exerts a continuous inhibitory influence on vascular tone. Whether the basal inhibitory endothelial influence might be affected in rat aorta exposed in vitro to a tolerance-inducing concentration of nitroglycerin was investigated in this study. It was found that the basal inhibitory influence, assessed as its inhibitory influence on norepinephrine-induced contraction, and as the contractile effect of N-nitro-L-arginine methyl ester or methylene blue, was the same in nitroglycerin-tolerant and control aortic rings. Our results give an indication that changes in basal inhibitory endothelial influence are not involved in the phenomena of nitrate tolerance and nitrate dependence.Key words: nitroglycerin, nitrates, tolerance, endothelium, nitric oxide.

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