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

Byon, Hyo-Jin; Ok, Seong-Ho; Lee, Soo Hee; Kang, Sebin; Cho, Young-Il; Han, Jeong Yeol; Sohn, Ju-Tae

doi:10.7150/ijms.17456

Cited by 10 publications

(7 citation statements)

References 21 publications

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“…23 However, Phen-induced vasoconstriction involves various calcium channels such as the store-operated calcium channel and voltage-operated calcium channel. 24 After the pretreatment with Phen (10 −6 M) in PA, Ach-induced vascular relaxations were partly dependent on the NO signaling pathway. ACh combining to the muscarinic receptor triggers an intracellular Ca 2+ increase in the endothelial cells, which activates endothelial NO synthase (eNOS) to synthesize NO, the potent endogenous vasodilator.…”

Section: Discussionmentioning

confidence: 99%

Synchronous detection of vascular tension and nitric oxide release in pulmonary artery: A combined application of confocal wire myograph with confocal laser scanning microscopy

Zhuang

Zhu

et al. 2020

Vascular

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Objectives To detect the vascular tension and nitric oxide (NO) release synchronously in mice pulmonary artery, we perform two experiments and present a novel application of confocal wire myograph coupled with the confocal laser scanning microscopy. Methods In the first experiment, viable endothelium-intact mouse pulmonary artery (outer diameter 100–300 μM) rings underwent a one-hour preincubation with a NO-specific fluorescent dye, 4-amino-5-methylamino-2′,7′-difluorofluorescein diacetate Calbiochem (2.5 μM), and then precontracted with phenylephrine (Phen, 10−6 M), and subsequently dilated in acetylcholine (ACh, 10−6 M – 10−4 M). The endothelium-dependent vasorelaxation and NO generation in pulmonary artery rings were simultaneously recorded. In the second experiment, after 30-min incubation with the former NO fluorescent dye, the qualified pulmonary artery rings were co-incubated for another 30 min with a nitric oxide synthase inhibitor, 10−4 M Nω-nitro-L-arginine-methyl-ester (L-NAME), and then pretreated with Phen (10−6 M) followed by ACh (10−5 M). The Ach-induced vasodilation and NO release were recorded simultaneously. Results ACh (10−6 M – 10−4 M) promoted pulmonary artery relaxation and intracellular NO release in a dose-dependent manner. Additionally, L-NAME (10−4 M) significantly attenuated the vasodilatation and the intracellular NO release. Conclusions This combined application visually confirms that the synchronous changes in Ach induced vasodilation and NO release, which provides a new method for cardiovascular research.

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Section: Discussionmentioning

confidence: 99%

Synchronous detection of vascular tension and nitric oxide release in pulmonary artery: A combined application of confocal wire myograph with confocal laser scanning microscopy

Zhuang

Zhu

et al. 2020

Vascular

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Section: Methodsmentioning

confidence: 99%

“…Human umbilical vein endothelial cells (EA.hy926 cells, American Type Culture Collection, Manassas, Virginia) were cultured in Endothelial Cell Medium (ScienCell Research Laboratories, Carlsbad, California) supplemented with 20% fetal bovine serum, 1% penicillin and streptomycin, and 1% endothelial cell growth supplement, as described previously. 23 Cells were plated onto gelatin (Difco, Becton Dickinson, New Jersey)-coated 100-mm culture dishes and incubated at 37 C in a humidified atmosphere containing 5% CO 2 with media change every 2 days. Upon reaching confluence, the cells were dissociated with 0.025% trypsin-ethylenediaminetetraacetic acid solution and split at a 1:4 ratio.…”

Section: Cell Culturementioning

confidence: 99%

“…Western blot analysis was carried out as described previously. 23 Briefly, cells were lysed in the PRO-PREP protein extraction solution to isolate the total cell extract by centrifugation at 16 000Âg for 15 minutes at 4 C. The protein concentrations were measured using the Bradford method. The protein samples to be loaded in the gel were prepared by mixing equal volumes of protein lysates with 2Â sodium dodecyl sulfate sample buffer (0.1 M Tris-HCl, 20% glycerol, 4% sodium dodecyl sulfate, and 0.01% bromophenol blue).…”

Section: Western Blot Analysismentioning

confidence: 99%

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Linolenic Acid Attenuates the Vasodilation Induced by Acetylcholine in Isolated Rat Aortae

Lee

Kim

et al. 2019

Dose-Response

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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.

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“…Human umbilical vein endothelial cells (HUVECs, EA.hy926 cells, American Type Culture Collection, Manassas, VA, USA) were cultured in Dulbecco's modified Eagle's medium (HyClone, GE Healthcare, UT, USA) supplemented with 10% heat-inactivated fetal bovine serum (Gibco, Life Technologies, NY, USA), 2 mM l-glutamine, 100 U/ml penicillin, and 100 µg/ml streptomycin as previously described [20,21]. Cells were plated in a 100-mm culture dish and incubated at 37°C in a humidified atmosphere containing 5% CO2.…”

Section: Cell Culturementioning

confidence: 99%

Nitric oxide-mediated inhibition of phenylephrine-induced contraction in response to hypothermia is partially modulated by endothelial Rho-kinase

Lee

Kim

et al. 2020

Int. J. Med. Sci.

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This study examined the possible upstream cellular signaling pathway associated with nitric oxide (NO)-mediated inhibition of phenylephrine-induced contraction in isolated rat aortae in response to mild hypothermia, with a particular focus on endothelial Rho-kinase. We examined the effects of mild hypothermia (33°C), wortmannin, N ω -nitro-L-arginine methyl ester (L-NAME), Y-27632, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and methylene blue, alone and combined, on phenylephrine-induced contraction in isolated rat aortae. Finally, we examined the effects of mild hypothermia, wortmannin, Y-27632 and L-NAME, alone and combined, on endothelial nitric oxide synthase (eNOS) and endothelial Rho-kinase membrane translocation induced by phenylephrine. Mild hypothermia attenuated phenylephrine-induced contraction only in endothelium-intact aortae. L-NAME, wortmannin, ODQ and methylene blue increased phenylephrine-induced contraction of endothelium-intact aortae pretreated at 33°C. Wortmannin did not significantly alter the L-NAME-induced enhancement of phenylephrine-induced maximal contraction of endotheliumintact aortae pretreated at 33°C. Wortmannin abolished the ability of Y-27632 to magnify the hypothermic inhibition of maximal phenylephrine-induced contraction. Wortmannin and L-NAME inhibited the enhancing effect of mild hypothermia on phenylephrine-induced eNOS phosphorylation. Y-27632 and L-NAME attenuated the enhancing effect of hypothermia on phenylephrine-induced endothelial Rho-kinase membrane translocation. The results suggest that hypothermia-induced, NO-dependent inhibition of phenylephrine-induced contraction is mediated by phosphoinositide 3-kinase and inhibited by endothelial Rho-kinase activation.

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

Cited by 10 publications

References 21 publications

Synchronous detection of vascular tension and nitric oxide release in pulmonary artery: A combined application of confocal wire myograph with confocal laser scanning microscopy

Synchronous detection of vascular tension and nitric oxide release in pulmonary artery: A combined application of confocal wire myograph with confocal laser scanning microscopy

Linolenic Acid Attenuates the Vasodilation Induced by Acetylcholine in Isolated Rat Aortae

Nitric oxide-mediated inhibition of phenylephrine-induced contraction in response to hypothermia is partially modulated by endothelial Rho-kinase

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