Inhibitory Effect of Fentanyl on Phenylephrine-Induced Contraction of the Rat Aorta

Park, Kyeong-Eon; Sohn, Ju-Tae; Jeong, Young Seok; Sung, Hui-Jin; Shin, Il Woo; Lee, Heon-Keun; Chung, Young-Kyun

doi:10.3349/ymj.2009.50.3.414

Cited by 7 publications

(8 citation statements)

References 30 publications

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“…This is the first study to provide laboratory evidence that dexmedetomidine attenuates alpha-1 adrenoceptor-mediated phenylephrine-induced contraction via blockade of the alpha-1 adrenoceptor. Previous studies have shown that fentanyl attenuates alpha-1 adrenoceptor-mediated phenylephrine-induced vasoconstriction 16 , 17 . Additionally, dexmedetomidine has been shown to inhibit phenylephrine-induced contraction in the internal mammary and gastroepiploic arteries, suggesting that dexmedetomidine may have an intrinsic affinity for the alpha-1 adrenoceptor 7 , 8 .…”

Section: Discussionmentioning

confidence: 96%

Dexmedetomidine Inhibits Phenylephrine-induced Contractions via Alpha-1 Adrenoceptor Blockade and Nitric Oxide Release in Isolated Rat Aortae

Byon

Lee

et al. 2017

Int. J. Med. Sci.

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The goal of this in vitro study was to examine the effect of the alpha-2 adrenoceptor agonist dexmedetomidine on phenylephrine (alpha-1 adrenoceptor agonist)-induced contraction in isolated rat aortae and to elucidate the associated cellular mechanisms, with a particular focus on alpha-1 adrenoceptor antagonism. Dexmedetomidine dose-response curves were generated in isolated endothelium-intact and endothelium-denuded rat aortae precontracted with phenylephrine or 5-hydroxytryptamine. Endothelium-denuded aortic rings were pretreated with either dexmedetomidine or the reversible alpha-1 adrenoceptor antagonist phentolamine, followed by post-treatment with the irreversible alpha-1 adrenoceptor blocker phenoxybenzamine. Control rings were treated with phenoxybenzamine alone. All rings were repeatedly washed with Krebs solution to remove all pretreatment drugs, including phenoxybenzamine, phentolamine and dexmedetomidine. Phenylephrine dose-response curves were then generated. The effect of rauwolscine on the dexmedetomidine-mediated change in phenylephrine-induced endothelial nitric oxide synthase (eNOS) phosphorylation in human umbilical vein endothelial cells was examined using western blotting. The magnitude of the dexmedetomidine-mediated inhibition of phenylephrine-induced contraction was higher in endothelium-intact aortae than in endothelium-denuded aortae or endothelium-intact aortae treated with Nω-nitro-L-arginine methyl ester. However, dexmedetomidine did not significantly alter 5-hydroxytryptamine-induced contraction. In further experiments, prazosin attenuated dexmedetomidine-induced contraction. Additionally, pretreatment with either dexmedetomidine plus phenoxybenzamine or phentolamine plus phenoxybenzamine produced greater phenylephrine-induced contraction than phenoxybenzamine alone, suggesting that dexmedetomidine protects aortae from the alpha-1 adrenoceptor blockade induced by phenoxybenzamine. Rauwolscine attenuated the dexmedetomidine-mediated enhancement of phenylephrine-induced eNOS phosphorylation. Taken together, these results suggest that dexmedetomidine attenuates phenylephrine-induced contractions via alpha-1 adrenoceptor blockade and endothelial nitric oxide release in the isolated rat aorta.

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Section: Discussionmentioning

confidence: 96%

Dexmedetomidine Inhibits Phenylephrine-induced Contractions via Alpha-1 Adrenoceptor Blockade and Nitric Oxide Release in Isolated Rat Aortae

Byon

Lee

et al. 2017

Int. J. Med. Sci.

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“…Four additional simulations were carried out at clinical concentrations, where the drug molecules were added randomly to the water phase. The concentrations used for propofol and fentanyl were 7.1 55 and 1.0 μM, 56 which corresponds to approximately 36 and 4 molecules, respectively.…”

Section: Discussionmentioning

confidence: 99%

Atomistic Molecular Dynamics Simulations of Propofol and Fentanyl in Phosphatidylcholine Lipid Bilayers

et al. 2020

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Atomistic molecular dynamics (MD) and steered MD simulations in combination with umbrella sampling methodology were utilized to study the general anesthetic propofol and the opioid analgesic fentanyl and their interaction with lipid bilayers, which is not yet fully understood. These molecules were inserted into two different fully hydrated phospholipid bilayers, namely, dioleoylphosphatidylcholine (DOPC) and dipalmitoylphosphatidylcholine (DPPC), to investigate the effects that these drugs have on the bilayer. We determined the role of the lipid chain length and saturation on the behavior of the two drugs. Pure, fully hydrated DOPC and DPPC bilayers were also simulated, and the results were in excellent agreement with the experimental values. Various structural and mechanical properties of each system, such as the area per lipid, area compressibility modulus, order parameter, lateral lipid diffusion, hydrogen bonds, and radial distribution functions, have been calculated to assess how the drug molecules affect the different bilayers. From the calculated results, we show that fentanyl and propofol generally follow similar trends in each bilayer but adopt different favorable positions close to the headgroup/chain interface at the carbonyl groups. Propofol was shown to selectively form hydrogen bonds at the carbonyl carbon in each bilayer, whereas fentanyl interacts with water molecules at the headgroup interface. From the calculated free-energy profiles, we determined that both molecules show a preference for the low-density, low-order acyl chain region of the bilayers and both significantly preferred the DOPC bilayer with propofol and fentanyl having energy minima at −6.66 and −43.07 kcal mol–1, respectively. This study suggests that different chain lengths and levels of saturation directly affect the properties of these two important molecules, which are seen to work together to control anesthesia in surgical applications.

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“…The anesthetic agent could not be used for this experiment because of the effect on vascular responses during organ bath investigations. [33][34][35] After cervical dislocation, thoracotomy was applied to obtain thoracic aorta. Tissues of rats were quickly removed and put into cold Krebs-Henseleit solution.…”

Section: Aortic Ring Isolations and Vascular Response Studiesmentioning

confidence: 99%

The impact of high fructose on cardiovascular system

et al. 2015

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The aim of this study was to evaluate the role of α-lipoic acid (α-LA) on oxidative damage and inflammation that occur in endothelium of aorta and heart while constant consumption of high-fructose corn syrup (HFCS). The rats were randomly divided into three groups with each group containing eight rats. The groups include HFCS, HFCS + α-LA treatment, and control. HFCS was given to the rats at a ratio of 30% of F30 corn syrup in drinking water for 10 weeks. α-LA treatment was given to the rats at a dose of 100 mg/kg/day orally for the last 6 weeks. At the end of the experiment, the rats were killed by cervical dislocation. The blood samples were collected for biochemical studies, and the aortic and cardiac tissues were collected for evaluation of oxidant–antioxidant system, tissue bath, and pathological examination. HFCS had increased the levels of malondialdehyde, creatine kinase MB, lactate dehydrogenase, and uric acid and showed significant structural changes in the heart of the rats by histopathology. Those changes were improved by α-LA treatment as it was found in this treatment group. Immunohistochemical expressions of tumor necrosis factor α and inducible nitric oxide synthase were increased in HFCS group, and these receptor levels were decreased by α-LA treatment. All the tissue bath studies supported these findings. Chronic consumption of HFCS caused several problems like cardiac and endothelial injury of aorta by hyperuricemia and induced oxidative stress and inflammation. α-LA treatment reduced uric acid levels, oxidative stress, and corrected vascular responses. α-LA can be added to cardiac drugs due to its cardiovascular protective effects against the cardiovascular diseases.

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Inhibitory Effect of Fentanyl on Phenylephrine-Induced Contraction of the Rat Aorta

Cited by 7 publications

References 30 publications

Dexmedetomidine Inhibits Phenylephrine-induced Contractions via Alpha-1 Adrenoceptor Blockade and Nitric Oxide Release in Isolated Rat Aortae

Dexmedetomidine Inhibits Phenylephrine-induced Contractions via Alpha-1 Adrenoceptor Blockade and Nitric Oxide Release in Isolated Rat Aortae

Atomistic Molecular Dynamics Simulations of Propofol and Fentanyl in Phosphatidylcholine Lipid Bilayers

The impact of high fructose on cardiovascular system

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