Isoeugenodilol: A vasorelaxant ?/?-adrenoceptor blocker with antioxidant activity

Yeh, Jwu‐Lai; Yang, Tzu Hsin; Liang, Jhy Chong; Huang, Yeun Chih; Lo, Yi-Ching; Wu, Jiunn Ren; Lin, Yu-Cheng; Chen, Ing Jun

doi:10.1002/1098-2299(20000901)51:1<29::aid-ddr4>3.0.co;2-2

Cited by 10 publications

(8 citation statements)

References 32 publications

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“…Isoeugenolol and isoeugenodilol were synthesized in our laboratory as previously described [15,16]. Propranolol, labetalol, prazosin, PD98059, PDGF-BB, vascular endothelial growth factor (VEGF), propidium iodide, fura-2/ AM, and smooth muscle a-actin antibodies were obtained from Sigma Chemical (St. Louis, MO).…”

Section: Methodsmentioning

confidence: 99%

“…1) as new third-generation b-adrenoceptor blockers with vasorelaxant and tracheal relaxant properties and having additional potentially antioxidant effects [15,16]. The oral administration of isoeugenodilol to conscious spontaneously hypertensive rats had long-lasting hypotensive and bradycardia effects, without causing the concomitant reflex changes in heart rate commonly associated with other antihypertensive agents.…”

Section: Introductionmentioning

confidence: 96%

“…The oral administration of isoeugenodilol to conscious spontaneously hypertensive rats had long-lasting hypotensive and bradycardia effects, without causing the concomitant reflex changes in heart rate commonly associated with other antihypertensive agents. We also further demonstrated that the vasorelaxant effect of isoeugenodilol could be related to a-adrenoceptor-and Ca 2+ channelblocking and K + channel-opening activities [16].…”

Section: Introductionmentioning

confidence: 99%

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Isoeugenodilol inhibits smooth muscle cell proliferation and neointimal thickening after balloon injury via inactivation of ERK1/2 pathway

et al. 2008

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The purpose of this study was to determine the efficacy and the possible mechanism of action of the synthesized drug isoeugenodilol (a new third-generation beta-adrenoceptor blocker) on the growth factor-induced proliferation of cultured rat vascular smooth muscle cells (VSMCs) and neointimal formation in a rat carotid arterial balloon injury model. Isoeugenodilol significantly inhibited 10% FBS, 20 ng/ml PDGF-BB, and 20 ng/ml vascular endothelial growth factor (VEGF)-induced proliferation. In accordance with these findings, isoeugenodilol revealed blocking of the FBS-inducible progression through the G(0)/G(1) to the S phase of the cell cycle in synchronized cells. Neointimal formation, measured 14 days after injury, was reduced by the oral administration of isoeugenodilol (10 mg/kg/day). In an in vitro assay, isoeugenodilol inhibited the migration of VSMCs stimulated by PDGF-BB. These findings indicate that isoeugenodilol shows an inhibitory potency on neointimal formation due to inhibition of both migration and proliferation of VSMCs. In addition, isoeugenodilol in concentration-dependent manner decreased the levels of phosphorylated ERK1/2 in both VSMCs and balloon-injured carotid arteries. The levels of phosphorylated MEK1/2 and Pyk2 as well as intracellular Ca(2+) and reactive oxygen species (ROS) were in concentration-dependent manner reduced by isoeugenodilol. Taken together, these results indicate that isoeugenodilol may suppress mitogen-stimulated proliferation and migration partially through inhibiting cellular ROS and calcium, and hence, through activation of the Pyk2-ERK1/2 signal pathway. This suggests that isoeugenodilol has potential for the prevention of atherosclerosis and restenosis.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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Isoeugenodilol inhibits smooth muscle cell proliferation and neointimal thickening after balloon injury via inactivation of ERK1/2 pathway

et al. 2008

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“…In hypertensive rats, isoeugenodilol, a chemical derivative of isoeugenol (the active component of AQUI-S TM ) has been shown to decrease mean blood pressure and heart rate in a dose dependent manner (Yeh et al 2000). This vasorelaxant activity was attributed to ability of isoeugenodilol to inhibit L-type Ca 2+ channels, receptor mediated Ca 2+ mobilisation and stimulation of K + channel opening.…”

Section: Proposed Models Of Anaesthetic Actionmentioning

confidence: 99%

Anaesthetic Effects on the Hepatic Portal Vein and on the Vascular Resistance of the Tail of the Chinook Salmon (Oncorhynchus tshawytscha)

Rothwell

Forster

2005

Fish Physiol Biochem

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We used blood vessel myography and a perfused tail preparation from the Chinook salmon (Oncorhynchus tshawytscha) to investigate the effect of 2 commercially used fish anaesthetics, AQUI-S TM and MS222, on vascular tone. Hepatic portal vein rings were exposed to 1 Â 10 )7 M adrenaline in the presence or absence of either AQUI-S TM or MS222 and changes in vessel tension measured. Tail preparations were perfused with saline containing increasing concentrations of either anaesthetic. Exposure to either anaesthetic did not alter the response of vessel rings to adrenaline in vitro. However, both anaesthetics caused a significant (P £ 0.05) decrease in vessel tension when compared to controls. In tail preparations, perfusion with either anaesthetic caused a significant (P £ 0.05) yet reversible, dose dependent decrease in vascular resistance. Further to this, it was found that for both anaesthetics there was a significant effect of fish holding time on the response of preparations, with fish that were acclimated for less than 1 week exhibiting less vasodilation in response to anaesthetic exposure. We conclude that commonly used concentrations of AQUI-S TM and MS222 can have a direct effect on vascular tone of salmon vessels, causing a significant but reversible vasodilation of vessels. This vasodilation may offset increases in haematocrit seen during anaesthesia in the whole animal, and in recovery prevent large rises in peripheral resistance associated with catecholamine release. A reduced vascular resistance may allow the heart to pump greater volumes of blood during recovery.

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“…Isolated Wistar rat thoracic aorta rings were used to evaluate the possible involvement of KMUP 880708 effects in α 1 -adrenoceptor mechanisms [Yeh et al, 2000b;2001]. Aorta preparations were mounted in a 10-ml or-gan bath and suspended in physiological solution at 37°C under a resting tension of 1.0 g. KMUP 880708 was added to the bath medium after a control concentration-response curve to norepinephrine (10 -10 to 3 × 10 -4 M) was obtained.…”

Section: Evalution Of a 1 -Adrenoceptor Antagonismmentioning

confidence: 99%

KMUP 880708: A vanyllilamide‐based β₁‐adrenoceptor antagonist with α‐adrenoceptor blocking and potassium channel opening activities

Chiu

Chen

et al. 2002

Drug Development Research

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A vanillylamide-based propanolamine derivative, KMUP 880708, was first investigated both in vivo and in vitro. KMUP 880708 (0.1, 0.5, 1.0, and 2.0 mg kg -1 , iv) produced dose-dependent hypotensive and bradycardia responses in pentobarbital-anesthetized Wistar rats. KMUP 880708 (0.1, 0.5, and 1.0 mg kg -1 , iv) also markedly inhibited both the tachycardia effects induced by (-)isoproterenol and arterial pressor responses induced by phenylephrine. KMUP 880708 competitively antagonized (-)isoproterenolinduced positive inotropic and chronotropic effects of the atria and tracheal relaxation responses on isolated guinea pig tissues. The apparent pA 2 values for KMUP 880708 was 7.82 ± 0.06 in the right atria, 7.51 ± 0.13 in the left atria, and 6.31 ± 0.07 in the trachea, respectively, indicating that KMUP 880708 was selective β 1 -adrenoceptor blocker. In thoracic aorta experiments, KMUP 880708 also produced a competitive antagonism of norepinephrine-induced contraction with pA 2 value of 7.92 ± 0.52, indicating that KMUP 880708 was α-adrenoceptor antagonist. In isolated rat thoracic aorta, KMUP 880708 more potently relaxed the contractions induced by phenylephrine (10 -5 M) than those by high K + (75 mM). KMUP 880708-induced relaxation was significantly reduced by endothelium removal and by exposure to L-N G -nitro arginine methyl ester (L-NAME, 1 and 3 × 10 -4 M), indomethacin (3 × 10 -5 M), methylene blue (10 -5 M) and 1H-[1,2,4]oxadiazolol[4,3,-a]quinoxalin-1-one (ODQ, 10 -6 M). The vasorelaxant effect of KMUP 880708 on phenylephrine-induced contraction was attenuated by the pretreatment with tetraethylammonium (TEA), glibenclamide, charybdotoxin, and apamin, but not by 4-aminopyridine (4-AP). In addition, KMUP 880708 inhibited phenylephrine-induced biphasic contraction and affected the fast-twitch phase more significantly than the slow tonic phase. In the radioligand-binding assay, the K i values of [ 3 H]CGP-12177 binding to rat ventricle and lung membranes were 15.14 and 524.81 nM, respectively, and the value of [ relaxation activities. Furthermore, the vasodilator effect of KMUP 880708 is attributed to the release of NO or NO-related substance from vascular endothelium. While the endothelium-independent mechanism involved in the relaxation of KMUP 880708 is probably linked to K + channel activation in these vessels. DrugDev. Res. 55:104-117, 2002.

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Isoeugenodilol: A vasorelaxant ?/?-adrenoceptor blocker with antioxidant activity

Cited by 10 publications

References 32 publications

Isoeugenodilol inhibits smooth muscle cell proliferation and neointimal thickening after balloon injury via inactivation of ERK1/2 pathway

Isoeugenodilol inhibits smooth muscle cell proliferation and neointimal thickening after balloon injury via inactivation of ERK1/2 pathway

Anaesthetic Effects on the Hepatic Portal Vein and on the Vascular Resistance of the Tail of the Chinook Salmon (Oncorhynchus tshawytscha)

KMUP 880708: A vanyllilamide‐based β₁‐adrenoceptor antagonist with α‐adrenoceptor blocking and potassium channel opening activities

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Isoeugenodilol: A vasorelaxant ?/?-adrenoceptor blocker with antioxidant activity

Cited by 10 publications

References 32 publications

Isoeugenodilol inhibits smooth muscle cell proliferation and neointimal thickening after balloon injury via inactivation of ERK1/2 pathway

Isoeugenodilol inhibits smooth muscle cell proliferation and neointimal thickening after balloon injury via inactivation of ERK1/2 pathway

Anaesthetic Effects on the Hepatic Portal Vein and on the Vascular Resistance of the Tail of the Chinook Salmon (Oncorhynchus tshawytscha)

KMUP 880708: A vanyllilamide‐based β1‐adrenoceptor antagonist with α‐adrenoceptor blocking and potassium channel opening activities

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Product

Resources

About

KMUP 880708: A vanyllilamide‐based β₁‐adrenoceptor antagonist with α‐adrenoceptor blocking and potassium channel opening activities