Role of potassium channels in the relaxant effect of levosimendan in guinea pig tracheal preparations

Eksert, Bilsen; Usta, Coşkun

doi:10.1016/s1734-1140(09)70032-5

Cited by 6 publications

(5 citation statements)

References 22 publications

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“…An important finding of the present study is the strong ability of levosimendan to protect against MCh-induced bronchospasm. The bronchoprotective potential demonstrated in the present study is in accordance with earlier results obtained with isolated guinea pig tracheal rings (12). In the guinea pig study, however, levosimendan was added to an organ bath containing a tracheal ring after establishing bronchospasm.…”

Section: Systemic Circulatory Effects Of Levosimendansupporting

confidence: 92%

Levosimendan prevents bronchoconstriction and adverse respiratory tissue mechanical changes in rabbits

Babik

Balogh

Südy

et al. 2017

American Journal of Physiology-Lung Cellular and Molecular Phys

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Levosimendan has a calcium-sensitizing effect in the myocardium and opens ATP-sensitive potassium channels (K) in vascular smooth muscle. Because airway smooth muscle also expresses K, we characterized the protective potential of levosimendan against increased airway and respiratory tissue resistances. Animals were administered levosimendan alone (), levosimendan after pretreatment with a K channel blocker (glibenclamide, ), glibenclamide only (), or solvent alone (dextrose, ). Airway resistance (R), tissue damping, and elastance were determined by forced oscillations under baseline conditions and following provocation tests with intravenous methacholine (MCh). Cardiac output (CO) was assessed by transpulmonary thermodilution. The same sequence of measurements was then repeated during intravenous infusion of levosimendan in and or glucose in and Sham treatments in and had no effect on lung responsiveness. However, levosimendan treatment in elevated CO and inhibited the MCh-induced airway responses [R changes of 87.8 ± 83% (SD) vs. 24.4 ± 16% at 4 μg·kg·min MCh, < 0.001], and in G (35.2 ± 12.7 vs. 25.2 ± 12.9%, < 0.05). The preventive affect of levosimendan against lung constriction vanished in the LG group. Levosimendan exerts a K-mediated potential to prevent bronchoconstriction and may prohibit adverse lung peripheral changes both in the small bronchi and the pulmonary parenchyma. The identification of a further pleiotropic property of levosimendan that is related to the pulmonary system is of particular importance for patients with decreased cardiorespiratory reserves for which simultaneous circulatory support is complemented with prevention of adverse respiratory events.

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Section: Systemic Circulatory Effects Of Levosimendansupporting

confidence: 92%

Levosimendan prevents bronchoconstriction and adverse respiratory tissue mechanical changes in rabbits

Babik

Balogh

Südy

et al. 2017

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Iberiotoxin, a selective blocker of BK Ca channels provoked a reduction in levosimendan-induced vasodilation in porcine coronary arteries, suggesting the involvement of BK Ca channel activation in levosimendan-induced vascular relaxation [19]. Similar combined mechanisms for smooth muscle relaxation have also been revealed in guinea pig tracheal preparations [5]. Moreover, our earlier results indicated that BK Ca channel activation was essential for OR-1896-induced coronary dilation, whereas these channels made only a limited contribution in the skeletal muscle arteries [6].…”

Section: Discussionmentioning

confidence: 90%

Levosimendan and its metabolite OR-1896 elicit KATP channel-dependent dilation in resistance arteries in vivo

Gődény

Pollesello

Édes

et al. 2013

Pharmacological Reports

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Background Levosimendan and its long-lived metabolite OR-1896 produce vasodilation in different types of vessels by activating ATP-sensitive (KATP) and other potassium channels. Methods In the present study we applied intravital videomicroscopy to investigate the in situ effects of levosimendan and OR-1896 on the diameters of real resistance arterioles (rat cremaster muscle arterioles with diameters of ~ 20 μm). Results Levosimendan and OR-1896 induced concentration-dependent (1 nM – 100 μM) dilations to similar extents in these arterioles (maximal dilation from 23 ± 2 to 33 ± 2 μm and from 22 ± 1 to 32 ± 1 μm, respectively). The arteriolar dilations induced by the selective KATP channel opener pinacidil (1 nM – 10 μM) (maximal dilation from 22 ± 4 μm to 35 ± 3 μm) were diminished in the presence of the selective KATP channel blocker – glibenclamide (5 μM) (maximal diameter attained: 22 ± 1 μm). Glibenclamide also counteracted the maximal dilations in response to levosimendan or OR-1896 (to 23 ± 3 μm or 22 ± 5 μm, respectively). Conclusions In conclusion, this is the first demonstration that levosimendan and OR-1896 elicit arteriolar dilation in vivo, via activation of KATP channels in real resistance vessels in the rat.

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“…Histamine-evoked broncho-constriction is due to the activation of H 1 -histaminergic receptors and is blocked by antihistaminergic drugs such as promethazine [31,32]. Whereas, KCl-induced broncho-constriction results from the depolarization of cell membrane which causes the augmentation of calcium influx through voltage operated calcium channels leading to the rise of intracellular calcium level [33]. Moreover, the acute and relatively refractory hyperkalemia can develop.…”

Section: Discussionmentioning

confidence: 99%

Dichrostachys cinerea (L.) Wight et Arn (Mimosaceae) hydro-alcoholic extract action on the contractility of tracheal smooth muscle isolated from guinea-pig

Aworet-Samseny¹,

Souza²,

Kpahé

et al. 2011

BMC Complement Altern Med

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BackgroundDichrostachys cinerea (L.) Wight et Arn. (Mimosaceae) is largely used in ethno-medically across Africa, and mainly employed for the treatment of asthma in Ivory Coast and Gabon. The paper analyses the relaxation induced by the methanolic extract of D. cinerea (Edici) in the guinea-pig trachea preparations (GPTPs). Purpose: This study aimed to bring out the scientific basis to the use of this plant leading to the validation of this phytomedicine.MethodThe aorta obtained from guinea-pigs was immediately placed in a Mac Ewen solution. Experiments were performed in preparations suspended between two L-shaped stainless steel hooks in a 10 ml organ bath containing Mac Ewen solution. The isometric contractile force of the aorta strips of guinea-pig were recorded by using a strain gauge. The different drugs were directly administered into the organ bath and the magnitude of GPTPs was evaluated.ResultsPhytochemical analysis of the methanolic extract of Dichrostachys cinerea (Edici) using chemical methods revealed the presence of flavenoids, tannins, sterols, triterpenes and polyphenols. Pharmacological studies performed in GPTPs show that of Dichrostachys cinerea (0.1 mg/ml - 2 mg/ml) evoked a broncho-constriction in GPTPs. Whereas, at concentration up to 2 mg/ml, Edici induced a significant dose-dependent relaxation in the GPTPs. KCl-, ACh- or histamine-evoked contractions of isolated trachea was significantly inhibited by increasing concentrations of Edici (3.5-10 mg/ml). Edici (10 mg/ml) as well as promethazine (0.25 mg/ml) significantly inhibited contractions induced by increasing concentrations of histamine (1×10-7-1×10-4mg/ml). In the presence of atropine at a concentration of 10-6mg/ml, contractile response curve (CRC) evoked by ACh (1×10-5-1×10-2 mg/ml) was significantly abolished in concentration-dependent manner. Edici did not significantly reduced ACh evoked contraction (10-5-10-2mg/ml).ConclusionThese observations suggest that Edici could act through two mechanisms: firstly by activation of β-adrenergic or histaminergic receptors; and secondly muscarinic receptors may not be greatly involved, that justifying the use of the extract in traditional Medicine in Africa.

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Role of potassium channels in the relaxant effect of levosimendan in guinea pig tracheal preparations

Cited by 6 publications

References 22 publications

Levosimendan prevents bronchoconstriction and adverse respiratory tissue mechanical changes in rabbits

Levosimendan prevents bronchoconstriction and adverse respiratory tissue mechanical changes in rabbits

Levosimendan and its metabolite OR-1896 elicit KATP channel-dependent dilation in resistance arteries in vivo

Dichrostachys cinerea (L.) Wight et Arn (Mimosaceae) hydro-alcoholic extract action on the contractility of tracheal smooth muscle isolated from guinea-pig

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