Vasorelaxant effect of mexiletine in mesenteric resistance arteries of rats

Dohi, Yasuaki; Kojima, M.; Sato, Koichi

doi:10.1111/j.1476-5381.1994.tb14790.x

Cited by 11 publications

(4 citation statements)

References 37 publications

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“…Contractions induced by depolarization with KCl have been shown to depend on Ca2`entry through voltage-dependent Ca2+ channels (Bolton, 1979). In previous experiments in this laboratory and others, it has been demonstrated that some class I antiarrhythmic drugs (i.e., propafenone, flecainide, quinidine, mexiletine, imipramine and desipramine) produced vasorelaxant effects that can be attributed to Ca2+ entry blockade (Carron et al, 1991;Perez Vizcaino et al, 1991;Dohi et al, 1994;Fernandez del Pozo et al, 1994). In the present study, quinidine and quinine inhibited in a concentrationdependent manner KCl-induced contractions, an effect that can be related to their ability to inhibit Ca2+ entry through L-type Ca21 channels.…”

Section: Discussionmentioning

confidence: 93%

“…Very recently, it has been reported that several class I antiarrhythmic drugs (e.g. Na+ channel blockers) such as propafenone (Carron et al, 1991), flecainide , quinidine , imipramine (Fernandez del Pozo et al, 1994) and mexiletine (Dohi et al, 1994) inhibited vascular smooth muscle contraction and this effect was accompanied by a decrease in Ca21 entry. Quinine also inhibited the contractions induced by KCl and angiotensin II in rabbit aorta (Cook et al, 1987) and the 45Ca2+ uptake induced by KCl in A7r5 cells (Cook & Quast, 1990).…”

Section: Introductionmentioning

confidence: 99%

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Stereoselective effects of the enantiomers, quinidine and quinine, on depolarization‐ and agonist‐mediated responses in rat isolated aorta

Pozo

Pérez‐Vizcaíno

Villamor

et al. 1996

British J Pharmacology

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1. The effects of the two enantiomers, quinidine and quinine, were studied on depolarization- and agonist-induced isometric contractions in rat isolated thoracic aortic rings. 2. Quinidine or quinine (10(-6)M-3 x 10(-4)M) produced a concentration-dependent relaxation of 80 mM KCl-contracted rings, the pD2 values being 4.89 and 4.23, respectively. Thus, quinidine was about 4-5 times more potent than quinine. 3. The voltage-dependence of quinidine- and quinine-induced inhibition was studied in rings that had been incubated in 5 or 40 mM KCl Ca(2+)-free solution and then contracted by changing the bath solution to 100 mM KCl and 2 mM Ca2+. The inhibitory effects of quinidine were significantly enhanced when the rings were preincubated in 40 mM KCl (depolarizing conditions), when compared to normally polarized rings. In contrast, the effects of quinine were similar in 5 or 40 mM KCl solution. 4. The antagonism of noradrenaline (NA)-induced contractions by low concentrations of quinidine (< 10(-4)M) and quinine (< 3 x 10(-4)M) was competitive, as demonstrated by the concentration-dependent parallel rightward shift of the NA concentration-response curves (pA2 values 6.20 and 5.68, respectively, P < 0.05). 5. At low concentrations (< or = 3 x 10(-5)M), quinidine and quinine did not shift the concentration-response curve to 5-hydroxytryptamine (5-HT) or endothelin-1, whereas at higher concentrations they produced a downward shift of these curves. Quinidine and quinine (> 10(-4)M) inhibited to a similar extent both the phasic (induced in Ca(2+)-free media) and tonic responses (after restoring extracellular Ca2+) induced by 5-HT. 6. In conclusion, quinidine and quinine produced a stereoselective inhibition of depolarization and NA-induced contractions, quinidine being more potent than quinine. The inhibition of KCl-induced contractions could be attributed to inhibition of Ca2+ entry. Both drugs also behaved as competitive antagonists of alpha 1D-adrenoceptors. At high concentrations, quinidine and quinine also decreased the contractions induced by endothelin-1 and 5-HT in a non-stereoselective manner.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Stereoselective effects of the enantiomers, quinidine and quinine, on depolarization‐ and agonist‐mediated responses in rat isolated aorta

Pozo

Pérez‐Vizcaíno

Villamor

et al. 1996

British J Pharmacology

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“…9 Vasoconstriction occurs following SCI, and restoration of posttraumatic spinal cord blood flow is an important therapeutic goal. Spinal cord white matter tracts may be damaged significantly by postinjury ischemia, 10,28 and is- The axoplasm shows some edema, and neurofilament (f) density is mildly decreased.…”

Section: Discussionmentioning

confidence: 99%

Effect of mexiletine on lipid peroxidation and early ultrastructural findings in experimental spinal cord injury

Kaptanoğlu¹,

Caner²,

Hs³

et al. 1999

Journal of Neurosurgery: Spine

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Object. The purpose of this study was to investigate the effect of mexiletine on lipid peroxidation and on ultrastructural findings after induced spinal cord injury (SCI). The authors also compared the activity of mexiletine to that of the well-known antioxidant, methylprednisolone sodium succinate (MPSS). Methods. Wistar rats were divided into seven groups, (Groups 1–7). Those in Groups 1 and 2 were control animals that underwent laminectomy only, after which nontraumatized spinal cord samples were obtained immediately (Group 1) and 2 hours postsurgery (Group 2). Spinal cord injury was induced in all other groups, and cord samples were obtained at 2 hours postsurgery. The rats in Group 3 underwent SCI alone; those in Group 4 received 30 mg/kg of MPSS intraperitoneally immediately after trauma was induced; and those in Groups 5, 6, and 7 received 1, 10, and 50 mg/kg of mexiletine, respectively, by intraperitoneal injection immediately after trauma was induced. Compared with the levels in control animals, lipid peroxidation was significantly elevated in rats in Groups 3 and 5, but there were no statistical differences among those in Groups 1, 2, 4, 6 and 7 in this regard. Compared with the findings in rats in Group 3, ultrastructural damage post-SCI was minor in rats in Groups 4 and 5, and there was even less damage evident in rats in Group 7. Conclusions. Analysis of these findings showed that administration of 50 mg/kg mexiletine significantly decreased the level of lipid peroxidation and protected spinal cord ultrastructure following SCI.

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“…In addition to blocking action on Na + channels, mexiletine exhibits the inhibitory effect on Ca 2+ channels. Thus, mexiletine causes relaxation of vascular and airway smooth muscles (Dohi et al 1994;Nakahara et al 2000a).…”

Section: Introductionmentioning

confidence: 99%

Mexiletine inhibits pharmacological actions of salbutamol through blockade of β 2 -adrenoceptors in bovine tracheal smooth muscle

Nakahara

Kubota

Sakamato

et al. 2001

Naunyn-Schmiedeberg's Archives of Pharmacology

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We examined the effects of mexiletine, a class Ib antiarrhythmic drug, on the changes in tension and adenosine 3',5'-cyclic monophosphate (cAMP) content induced by salbutamol and forskolin in bovine tracheal smooth muscle. Salbutamol (0.0001-1 microM) produced concentration-dependent relaxation in bovine tracheal smooth muscle contracted with methacholine (0.3 microM). Mexiletine (5-500 microM) caused the rightward shifts of concentration-response curves for the relaxant responses to salbutamol in a concentration-dependent manner. Mexiletine (5, 50 or 500 microM) did not change basal cAMP levels, whereas it concentration-dependently attenuated the salbutamol (0.1 microM)-induced cAMP accumulation. On the other hand, mexiletine (500 microM) did not change the concentration-response curves for the relaxant responses to forskolin (0.001-10 microM). Mexiletine slightly but significantly (P<0.05) increased forskolin (1 microM)-induced cAMP accumulation. In radioligand binding experiments, mexiletine concentration-dependently displaced the specific binding of [125I]cyanopindolol to beta-adrenoceptors on bovine tracheal smooth muscle membranes. By contrast, lidocaine, another class Ib antiarrhythmic drug, did not change the binding of [125I]cyanopindolol. These results demonstrate that mexiletine prevents the binding of beta2-adrenoceptor agonists to their receptors and thereby suppresses manifestation of subsequent pharmacological responses.

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Vasorelaxant effect of mexiletine in mesenteric resistance arteries of rats

Cited by 11 publications

References 37 publications

Stereoselective effects of the enantiomers, quinidine and quinine, on depolarization‐ and agonist‐mediated responses in rat isolated aorta

Stereoselective effects of the enantiomers, quinidine and quinine, on depolarization‐ and agonist‐mediated responses in rat isolated aorta

Effect of mexiletine on lipid peroxidation and early ultrastructural findings in experimental spinal cord injury

Mexiletine inhibits pharmacological actions of salbutamol through blockade of β 2 -adrenoceptors in bovine tracheal smooth muscle

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