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2.
Int J Mol Sci ; 21(5)2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32143531

RESUMO

The goal of this study was to examine the effect of lipid emulsion on the vasodilation induced by ATP-sensitive potassium (KATP) channels in isolated rat aortae and the underlying mechanism. The effects of Intralipid, containing 100% long-chain fatty acids, and Lipofundin MCT/LCT, containing 50% long-chain fatty acids plus 50% medium-chain fatty acids, on the vasodilation induced by levcromakalim in endothelium-intact aorta with or without NW-nitro-L-arginine methyl ester (L-NAME) and in endothelium-denuded aorta were examined. The effects of L-arginine, L-NAME, glibenclamide, and Lipofundin MCT/LCT, alone or combined, on the levcromakalim-induced vasodilation were examined. Lipofundin MCT/LCT inhibited the levcromakalim-induced vasodilation of isolated endothelium-intact aortae, whereas Intralipid did not. In addition, Lipofundin MCT/LCT had no effect on the levcromakalim-induced vasodilation of endothelium-denuded rat aortae and endothelium-intact aortae with L-NAME. L-arginine and Lipofundin MCT/LCT produced more levcromakalim-induced vasodilation than Lipofundin MCT/LCT alone. Glibenclamide inhibited levcromakalim-induced vasodilation. Levcromakalim did not significantly alter endothelial nitric oxide synthase phosphorylation, whereas Lipofundin MCT/LCT decreased cyclic guanosine monophosphate. Lipofundin MCT/LCT did not significantly alter levcromakalim-induced membrane hyperpolarization. Taken together, these results suggest that Lipofundin MCT/LCT inhibits the vasodilation induced by levcromakalim by inhibiting basally released endothelial nitric oxide, which seems to occur through medium-chain fatty acids.

3.
Dose Response ; 17(4): 1559325819894148, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31839761

RESUMO

This study aims to examine the effect of linolenic acid on the vasodilation or vasoconstriction induced by acetylcholine and bupivacaine in isolated rat aortae and its underlying mechanism. The effect of linolenic acid on the vasodilation induced by acetylcholine, the calcium ionophore A23187, sodium nitroprusside, and 8-bromoguanosine 3',5'-cyclic monophosphate sodium salt (bromo-cyclic guanosine monophosphate [bromo-cGMP]) in endothelium-intact and endothelium-denuded aortae was examined. Linolenic acid inhibited vasodilation induced by acetylcholine, calcium ionophore A23187, and sodium nitroprusside. However, this fatty acid increased bromo-cGMP-induced vasodilation in endothelium-denuded aortae. Linolenic acid increased bupivacaine-induced contraction in endothelium-intact aortae, whereas it decreased bupivacaine-induced contraction in endothelium-intact aortae with Nω-nitro-l-arginine methyl ester and endothelium-denuded aortae. Linolenic acid inhibited acetylcholine- and bupivacaine-induced phosphorylation of endothelial nitric oxide synthase. Sodium nitroprusside increased cGMP in endothelium-denuded aortic strips, whereas bupivacaine decreased cGMP in endothelium-intact aortic strips. Linolenic acid decreased cGMP levels produced by bupivacaine and sodium nitroprusside. Together, these results suggest that linolenic acid inhibits acetylcholine-induced relaxation by inhibiting a step just prior to nitric oxide-induced cGMP formation. In addition, linolenic acid-mediated inhibition of vasodilation induced by a toxic concentration (3 × 10-4 M) of bupivacaine seems to be partially associated with inhibition of the nitric oxide-cGMP pathway.

4.
Korean J Pain ; 27(3): 229-38, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25031808

RESUMO

BACKGROUND: A toxic dose of bupivacaine produces vasodilation in isolated aortas. The goal of this in vitro study was to investigate the cellular mechanism associated with bupivacaine-induced vasodilation in isolated endotheliumdenuded rat aortas precontracted with phenylephrine. METHODS: Isolated endothelium-denuded rat aortas were suspended for isometric tension recordings. The effects of nifedipine, verapamil, iberiotoxin, 4-aminopyridine, barium chloride, and glibenclamide on bupivacaine concentration-response curves were assessed in endothelium-denuded aortas precontracted with phenylephrine. The effect of phenylephrine and KCl used for precontraction on bupivacaine-induced concentration-response curves was assessed. The effects of verapamil on phenylephrine concentration-response curves were assessed. The effects of bupivacaine on the intracellular calcium concentration ([Ca(2+)]i) and tension in aortas precontracted with phenylephrine were measured simultaneously with the acetoxymethyl ester of a fura-2-loaded aortic strip. RESULTS: Pretreatment with potassium channel inhibitors had no effect on bupivacaine-induced relaxation in the endothelium-denuded aortas precontracted with phenylephrine, whereas verapamil or nifedipine attenuated bupivacaine-induced relaxation. The magnitude of the bupivacaine-induced relaxation was enhanced in the 100 mM KCl-induced precontracted aortas compared with the phenylephrine-induced precontracted aortas. Verapamil attenuated the phenylephrine-induced contraction. The magnitude of the bupivacaine-induced relaxation was higher than that of the bupivacaine-induced [Ca(2+)]i decrease in the aortas precontracted with phenylephrine. CONCLUSIONS: Taken together, these results suggest that toxic-dose bupivacaine-induced vasodilation appears to be mediated by decreased calcium sensitization in endothelium-denuded aortas precontracted with phenylephrine. In addition, potassium channel inhibitors had no effect on bupivacaine-induced relaxation. Toxic-dose bupivacaine- induced vasodilation may be partially associated with the inhibitory effect of voltage-operated calcium channels.

5.
Int J Biol Sci ; 10(4): 367-76, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24719554

RESUMO

Intravenous lipid emulsions (LEs) are effective in the treatment of toxicity associated with various drugs such as local anesthetics and other lipid soluble agents. The goals of this study were to examine the effect of LE on left ventricular hemodynamic variables and systemic blood pressure in an in vivo rat model, and to determine the associated cellular mechanism with a particular focus on nitric oxide. Two LEs (Intralipid(®) 20% and Lipofundin(®) MCT/LCT 20%) or normal saline were administered intravenously in an in vivo rat model following induction of anesthesia by intramuscular injection of tiletamine/zolazepam and xylazine. Left ventricular systolic pressure (LVSP), blood pressure, heart rate, maximum rate of intraventricular pressure increase, and maximum rate of intraventricular pressure decrease were measured before and after intravenous administration of various doses of LEs or normal saline to an in vivo rat with or without pretreatment with the non-specific nitric oxide synthase inhibitor N(ω)-nitro-L-arginine-methyl ester (L-NAME). Administration of Intralipid(®) (3 and 10 ml/kg) increased LVSP and decreased heart rate. Pretreatment with L-NAME (10 mg/kg) increased LSVP and decreased heart rate, whereas subsequent treatment with Intralipid(®) did not significantly alter LVSP. Intralipid(®) (10 ml/kg) increased mean blood pressure and decreased heart rate. The increase in LVSP induced by Lipofundin(®) MCT/LCT was greater than that induced by Intralipid(®). Intralipid(®) (1%) did not significantly alter nitric oxide donor sodium nitroprusside-induced relaxation in endothelium-denuded rat aorta. Taken together, systemic blockage of nitric oxide synthase by L-NAME increases LVSP, which is not augmented further by intralipid(®).


Assuntos
Arginina/análogos & derivados , Pressão Sanguínea/efeitos dos fármacos , Ventrículos do Coração/efeitos dos fármacos , Óxido Nítrico Sintase/antagonistas & inibidores , Fosfolipídeos/farmacologia , Óleo de Soja/farmacologia , Animais , Arginina/farmacologia , Combinação de Medicamentos , Emulsões/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Masculino , Óxido Nítrico , Ratos , Ratos Sprague-Dawley , Sorbitol/farmacologia , Tiletamina/farmacologia , Xilazina/farmacologia , Zolazepam/farmacologia
6.
Korean J Anesthesiol ; 63(4): 376-7, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23115696
7.
Korean J Pain ; 25(3): 188-90, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22787550

RESUMO

Kikuchi's disease (KD) is an idiopathic and self-limiting necrotizing lymphadenitis that predominantly occurs in young females. It is common in Asia, and the cervical lymph nodes are commonly involved. Generally, KD has symptoms and signs of lymph node tenderness, fever, and leukocytopenia, but there are no reports on treatment for the associated myofacial pain. We herein report a young female patient who visited a pain clinic and received a trigger point injection 2 weeks before the diagnosis of KD. When young female patients with myofascial pain visit a pain clinic, doctors should be concerned about the possibility of KD, which is rare but can cause severe complications.

8.
Can J Physiol Pharmacol ; 90(7): 863-72, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22702717

RESUMO

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: N(ω)-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.


Assuntos
Anestésicos Locais/farmacologia , Aorta/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Mepivacaína/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacos , Animais , Aorta/metabolismo , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Células Cultivadas , GMP Cíclico/metabolismo , Endotélio Vascular/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Masculino , Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Óxido Nítrico/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Ratos , Ratos Sprague-Dawley , Vasodilatação/efeitos dos fármacos
9.
Korean J Anesthesiol ; 61(6): 499-505, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22220228

RESUMO

BACKGROUND: Ulinastatin has anti-inflammatory properties and protects organs from ischemia/reperfusion-induced injury. The aim of this study was to investigate whether ulinastatin provides a protective effect on a regional myocardial ischemia/reperfusion injury in an in vivo rat heart model and to determine whether the anti-inflammatory response is related to its myocardial protective effect. METHODS: Rats were randomized to two groups. One group is received ulinastatin (50,000 U/kg or 100,000 U/kg) diluted in normal saline and the other group is received normal saline, which was administered intraperitoneally 30 min before the ischemic insult. Reperfusion after 30 min of ischemia of the left coronary artery territory was applied. Hemodynamic measurements were recorded serially during 6 h after reperfusion. After the 6 h reperfusion, myocardial infarct size, cardiac enzymes, myeloperoxidase activity, and inflammatory cytokine levels were compared between the ulinastatin treated and untreated groups. RESULTS: Ulinastatin improved cardiac function and reduced infarct size after regional ischemia/reperfusion injury. Ulinastatin significantly attenuated tumor necrosis factor-α expression and reduced myeloperoxidase activity. CONCLUSIONS: Ulinastatin showed a myocardial protective effect after regional ischemia/reperfusion injury in an in vivo rat heart model. This protective effect of ulinastatin might be related in part to ulinastatin's ability to inhibit myeloperoxidase activity and decrease expression of tumor necrosis factor-α.

10.
Korean J Anesthesiol ; 58(4): 378-82, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20508796

RESUMO

BACKGROUND: It is well known that propofol protects myocardium against myocardial ischemia/reperfusion injury in the rat heart model. The aim of this study was to investigate whether propofol provides a protective effect against a regional myocardial ischemia/reperfusion injury in an in vivo rat heart model after 48 h of reperfusion. METHODS: Rats were subjected to 25 min of left coronary artery occlusion followed by 48 h of reperfusion. The sham group received profopol without ischemic injury. The control group received normal saline with ischemia/reperfusion injury. The propofol group received profopol with ischemia/reperfusion injury. The intralipid group received intralipid with ischemia/reperfusion injury. A microcatheter was advanced into the left ventricle and the hemodynamic function was evaluated. The infarct size was determined by triphenyltetrazolium staining. The serum level of cardiac troponin-I (cTn-I) was determined by ELISA (enzyme-linked immunosorbent assay). RESULTS: Propofol demonstrated protective effects on hemodynamic function and infarct size reduction. In the propofol group, the +dP/d(tmax) (P = 0.002) was significantly improved compared to the control group. The infarct size was 49.8% of the area at risk in the control group, and was reduced markedly by administration of propofol to 32.6% in the propofol group (P = 0.014). The ischemia/reperfusion-induced serum level of cTn-I was reduced by propofol infusion during the peri-ischemic period (P = 0.0001). CONCLUSIONS: Propofol, which infused at clinically relevant concentration during the peri-ischemic period, has delayed myocardial protective effect after regional myocardial ischemia/reperfusion injury in an in vivo rat heart model after 48 h of reperfusion.

11.
Reg Anesth Pain Med ; 35(2): 145-7, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20301821

RESUMO

BACKGROUND AND OBJECTIVES: Spinal anesthesia and intrathecal clonidine are known to have hypnotic effects. We investigated the effect of spinal anesthesia and intrathecal clonidine on the requirement of propofol for sedation. METHODS: Sixty adult patients scheduled for stripping and ligation of varicose veins under local or spinal anesthesia were enrolled in this study. Group 1 included patients given local anesthesia, group 2 included patients given spinal anesthesia, and group 3 included patients given spinal anesthesia with 75 microg of clonidine. Target-controlled infusion of propofol was started to achieve a target concentration of 1 and 1.5 microg/mL, and the mean bispectral index (BIS) for 1 min was checked after an effect site concentration (Ce) of 1 and 1.5 microg/mL propofol was reached. In addition, the Ce of propofol was documented when the mean BIS for 1 min reached 80 and 70 for the 3 groups, respectively, during the observation period. RESULTS: The BIS at 1 microg/mL propofol Ce was 87 (group 1), 80 (group 2), and 69 (group 3). The BIS at 1.5 microg/mL propofol Ce was 76, 64, and 51, respectively. The Ce of propofol when the BIS first reached 80 was 1.4, 1.1, and 0.7 microg/mL, respectively. The Ce of propofol when the BIS first reached 70 was 1.7, 1.4, and 0.9 microg/mL, respectively. CONCLUSIONS: Spinal anesthesia and intrathecal clonidine might reduce the requirement of propofol for sedation. Our study showed target concentrations of propofol for sedation of 1.4 to 1.7 using local anesthesia only, 1.1 to 1.4 using spinal anesthesia with bupivacaine, and 0.7 to 0.9 microg/mL using spinal anesthesia with bupivacaine and 75 microg of clonidine


Assuntos
Analgésicos/administração & dosagem , Raquianestesia , Clonidina/administração & dosagem , Hipnóticos e Sedativos/administração & dosagem , Propofol/administração & dosagem , Adulto , Bupivacaína/administração & dosagem , Humanos , Injeções Espinhais , Masculino , Pessoa de Meia-Idade , Varicocele/cirurgia , Adulto Jovem
12.
Yonsei Med J ; 50(3): 414-21, 2009 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-19568605

RESUMO

PURPOSE: Fentanyl was reported to inhibit the alpha(1)-adrenoceptor agonist-induced contraction. The goal of this in vitro study was to identify the alpha(1)-adrenoceptor subtype primarily involved in the fentanyl-induced attenuation of phenylephrine-induced contraction in isolated endothelium-denuded rat aorta. MATERIALS AND METHODS: Aortic rings were suspended in order to record isometric tension. Concentration-response curves for phenylephrine (10(-9) to 10(-5) M) were generated in the presence or absence of one of the following drugs: fentanyl (3 x 10(-7), 10(-6), 3 x10(-6) M), 5-methylurapidil (3 x10(-8), 10(-7), 3 x 10(-7) M), chloroethylclonidine (10(-5) M) and BMY 7378 (3 x 10(-9), 10(-8), 3 x 10(-8) M). Phenylephrine concentration-response curves were generated in the presence or absence of fentanyl in rings pretreated with either 3 x10(-9) M prazosin, 10(-9) M 5-methylurapidil or 3 x 10(-9) M BMY 7378. RESULTS: Fentanyl (10(-6), 3 x 10(-6) M) attenuated phenylephrine-induced contraction in the rat aorta. 5-Methylurapidil and BMY 7378 produced a parallel rightward shift in the phenylephrine concentration-response curve. The pA(2) values for 5-methylurapidil and BMY 7378 were estimated to be 7.71 +/- 0.15 and 8.99 +/- 0.24, respectively. Fentanyl (10(-6) M) attenuated phenylephrine-induced contraction in rings pretreated with 10(-9) M 5-methylurapidil, but did not alter the rings when pretreated with 3 x 10(-9) M BMY 7378. Pretreatment of the rings with chloroethylclonidine showed a 72.9 +/- 2.3% reduction in phenylephrine-induced maximal contraction. CONCLUSION: The results suggest that fentanyl attenuates phenylephrine-induced contraction by inhibiting the pathway involved in the alpha(1D)-adrenoceptor-mediated contraction of the rat aorta.


Assuntos
Agonistas alfa-Adrenérgicos/farmacologia , Antagonistas Adrenérgicos alfa/farmacologia , Aorta/efeitos dos fármacos , Fentanila/farmacologia , Fenilefrina/farmacologia , Vasoconstrição/efeitos dos fármacos , Animais , Clonidina/análogos & derivados , Clonidina/farmacologia , Técnicas In Vitro , Masculino , Piperazinas/farmacologia , Ratos , Ratos Sprague-Dawley
13.
Can J Anaesth ; 54(6): 453-60, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17541074

RESUMO

PURPOSE: Tramadol produces a conduction block similar to lidocaine by exerting a local anesthetic-like effect. The aims of this in vitro study were to determine the effects of tramadol on the vasorelaxant response induced by the adenosine triphosphate-sensitive K(+) (K(ATP)) channel opener, levcromakalim, in an endothelium-denuded rat aorta, and to determine whether this effect of tramadol is stereoselective. METHODS: The effects of tramadol (racemic, R(-) and S(+): 10(-6), 10(-5), 5 x 10(-5) M), and glibenclamide on the levcromakalim dose-response curve were assessed in aortic rings that had been pre-contracted with phenylephrine. In the rings pretreated independently with naloxone, and glibenclamide, the levcromakalim dose-response curves were generated in the presence or absence of tramadol. The effect of tramadol on the dose-response curve of diltiazem was assessed. RESULTS: Racemic, R(-) and S(+) tramadol (10(-5), 5 x 10(-5) M) attenuated (P < 0.0001) levcromakalim-induced relaxation in the ring with or without naloxone in a dose-dependent manner. The magnitude of the R(-)-tramadol-induced attenuation of vasorelaxant response induced by levcromakalim was greater (P < 0.05) than that induced by S(+)-tramadol. Glibenclamide almost abolished the levcromakalim-induced relaxation. Tramadol, 5 x 10(-5) M, did not significantly alter the diltiazem-induced relaxation. CONCLUSION: These results suggest that a supraclinical dose (10(-5) M) of tramadol [racemic, R(-) and S(+)] attenuates the vasorelaxation mediated by the K(ATP) channels in the rat aorta. The R(-) tramadol-induced attenuation of vasorelaxation induced by levcromaklim was more potent than that induced by S(+) tramadol. This attenuation is independent of opioid receptor activation.


Assuntos
Analgésicos Opioides/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Canais de Potássio Corretores do Fluxo de Internalização/fisiologia , Tramadol/farmacologia , Analgésicos Opioides/química , Animais , Aorta/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/farmacologia , Cromakalim/farmacologia , Interpretação Estatística de Dados , Diltiazem/farmacologia , Relação Dose-Resposta a Droga , Glibureto/farmacologia , Hipoglicemiantes/farmacologia , Técnicas In Vitro , Canais KATP , Masculino , Relaxamento Muscular/efeitos dos fármacos , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio Corretores do Fluxo de Internalização/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Estereoisomerismo , Tramadol/química
14.
Anesth Analg ; 103(2): 366-71, table of contents, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16861418

RESUMO

Tramadol, a combination of R(-) and S(+) enantiomers, inhibits both the acetylcholine-mediated response of muscarinic receptors and the muscarine-induced accumulation of cyclic guanosine monophosphate. Our goals in this in vitro study were to investigate the effects of tramadol on endothelium-dependent relaxation induced by acetylcholine, to determine whether this effect of tramadol is stereoselective, and to elucidate the associated cellular mechanism in rat aorta. In endothelium-intact rings precontracted with phenylephrine with or without naloxone, dose-response curves for acetylcholine, histamine, and calcium ionophore A23187 were generated in the presence and absence of tramadol (racemic, R(-) and S(+)). Sodium nitroprusside dose-response curves were generated in the presence and absence of racemic tramadol. Racemic tramadol (5 x 10(-5) 10(-4) M) attenuated acetylcholine-induced relaxation in the rings with or without naloxone. R(-) tramadol, 5 x 10(-5) M, attenuated acetylcholine-induced relaxation, whereas S(+) tramadol, 5 x 10(-5) M, did not. Racemic tramadol (10(-4) M) had no effect on dose-response curves for calcium ionophore A23187 or sodium nitroprusside. Taken together, these results indicate that tramadol, at a supraclinical dose (5 x 10(-5) M), stereoselectively attenuates endothelium-dependent relaxation via an inhibitory effect at levels proximal to nitric oxide synthase activation on a pathway involving nonspecific endothelial receptor activation.


Assuntos
Analgésicos Opioides/farmacologia , Aorta Torácica/efeitos dos fármacos , Endotélio Vascular/fisiologia , Tramadol/farmacologia , Vasodilatação/efeitos dos fármacos , Acetilcolina/farmacologia , Animais , Aorta Torácica/fisiologia , Relação Dose-Resposta a Droga , Técnicas In Vitro , Masculino , Óxido Nítrico/fisiologia , Ratos , Ratos Sprague-Dawley , Estereoisomerismo
15.
Anesth Analg ; 102(3): 682-9, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16492815

RESUMO

In this in vitro study we examined the effects of diazepam on a phenylephrine-induced contraction in rat aorta and determined the associated cellular mechanism focusing on the endothelium-derived vasodilators. The concentration-response curves for phenylephrine and potassium chloride were generated in the presence or absence of diazepam. Phenylephrine concentration-response curves were generated from the endothelium-intact rings pretreated independently with N(W)-nitro-L-arginine methyl ester, PK 11195, tetraethylammonium, and indomethacin in the presence or absence of diazepam. Diazepam (7 x 10(-7) M) attenuated the phenylephrine-induced contraction in the endothelium-intact rings, whereas a large dose (5 x 10(-6) M) of diazepam attenuated the phenylephrine-induced contraction in the aortic rings with or without the endothelium. A pretreatment with the N(W)-nitro-L-arginine methyl ester completely abolished the diazepam (7 x 10(-7) M)-induced attenuation of the phenylephrine concentration-response curve, as well as the diazepam (5 x 10(-6) M)-induced attenuation of the maximal contractile response to phenylephrine. The N(W)-nitro-L-arginine methyl ester (10(-4) M)-induced contraction was enhanced in the rings pretreated with diazepam (5 x 10(-6) M). These results indicate that a supraclinical concentration of diazepam attenuates phenylephrine-induced contraction by increasing endothelial nitric oxide activity and directly affecting vascular smooth muscle.


Assuntos
Aorta Torácica/efeitos dos fármacos , Diazepam/farmacologia , Fenilefrina/farmacologia , Vasoconstrição/efeitos dos fármacos , Animais , Aorta Torácica/fisiologia , Relação Dose-Resposta a Droga , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Técnicas In Vitro , Masculino , Fenilefrina/antagonistas & inibidores , Ratos , Ratos Sprague-Dawley , Vasoconstrição/fisiologia
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