Potassium Channel-Related Relaxation by Levosimendan in the Human Internal Mammary Artery

Yıldız, Oğuzhan; Seyrek, Melik; Yıldırım, Vedat; Demirkılıç, Ufuk; Nacitarhan, Cahit

doi:10.1016/j.athoracsur.2005.12.057

Cited by 14 publications

(18 citation statements)

References 22 publications

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“…A single 0.5 mg oral dose of levosimendan produces a peak plasma concentration of 20 ng / ml (0.07 µM) (34). This finding is in contrast with pD 2 values for levosimendan obtained in IMA (6.80 and 6.06) and porcine coronary artery (3.64) (6,26,35). Previously, it was reported that although levosimendan given in doses of 0.25 and 0.5 mg increased left ventricular function in ischemic heart disease, a significant decrease in total peripheral resistance was seen only after 2 and 4 mg (36).…”

Section: Involvement Of Kcontrasting

confidence: 54%

“…In this setting, resting membrane potential approaches the equilibrium potential of K + , thereby attenuating the hyperpolarizing actions of K + -channel activation. We have recently shown that levosimendan relaxes human internal mammary artery (IMA) through opening of K ATP channels (26). Previous studies suggested that K ATP , K V , and BK Ca channels are present in IMA (27 -29).…”

Section: Involvement Of Kmentioning

confidence: 99%

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Vasodilating Mechanisms of Levosimendan: Involvement of K+ Channels

Yıldız

2007

J Pharmacol Sci

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Abstract. Levosimendan, a novel agent developed for the treatment of acute and decompensated heart failure, exerts potent positive inotropic action and peripheral vasodilatory effects. The mechanism of vasodilation by levosimendan may involve reduction of Ca 2+ sensitivity of contractile proteins in vascular smooth muscle, the lowering of intracellular free Ca 2+, the potential inhibition of phosphodiesterase (PDE) III, and an opening of K + channels. Although the importance and relative contribution of each of these mechanisms of vasorelaxation is unclear and may be different in various vessels and dependent on the dose of levosimendan, the important roles of K + -channel opening and Ca 2+ desensitization in vascular smooth muscle are obvious, whereas the role of PDE inhibition remains to be defined. This review article briefly discusses the current research data on the mechanism of levosimendan-induced vasodilation with an emphasis on the types of the blood vessels and the K + channels. It also summarizes the current experimental and clinical knowledge of the use of levosimedan in the treatment of heart failure.

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Section: Involvement Of Kcontrasting

confidence: 54%

Section: Involvement Of Kmentioning

confidence: 99%

Vasodilating Mechanisms of Levosimendan: Involvement of K+ Channels

Yıldız

2007

J Pharmacol Sci

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“…The fact that PA rings without functional endothelium (≤ 20% of tension decrease during ACh exposition) showed similar doseresponse curves of an accumulative addition of levosimendan, would make the levosimendan relaxant effects endotheliumindependent, like in others vascular beds [19,20]. Mesenteric rings relaxation to levosimendan showed similar dose-response parameters of other systemic vascular beds as the human internal mammary arteries (pD2 6.8 ± 0.1 and Emax 75 ± 5%) [20].…”

Section: Discussionmentioning

confidence: 54%

“…Mesenteric rings relaxation to levosimendan showed similar dose-response parameters of other systemic vascular beds as the human internal mammary arteries (pD2 6.8 ± 0.1 and Emax 75 ± 5%) [20].…”

Section: Discussionmentioning

confidence: 79%

Preferential Vasodilator Effects of Levosimendan in Resistance Pulmonary Arteries in a Rodent Pulmonary Embolism Model

Bedo

Grignola

2017

ICFJ

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IntroductionThe pulmonary vasculature consists of large, elastic, extraparenchymal conduit pulmonary arteries (CPA, order 1 to 2) that arise from the sixth aortic arch and small, muscular resistance intrapulmonary arteries (RPA, ≥ 4th order), that originate from the mesenchymal lung bud by capillary plexus expansion [1]. This subdivision is associated with different response to several stimuli. While CPA dilates or fails to constrict to hypoxia, RPA is responsible for hypoxic pulmonary vasoconstriction, control the regional distribution of blood flow and largely determine pulmonary vascular resistance. This functional difference mainly depends on the distribution of electrophysiologically distinct myocytes in CPAs and RPAs arteries [1,2].Levosimendan is a positive inotropic agent (by increasing the sensitivity of troponin C to calcium) with vasodilating properties (by lowering of intracellular free Ca++, opening of different potassium channels and the inhibition of phosphodiesterase type III), also termed inodilator [3,4]. There are several animals studies in different acute pulmonary hypertension (PH) models secondary to thromboxane A2 infusion [5], endotoxemia [6], acute pulmonary embolism (PE) [7,8], and hypoxia [9] and some clinical studies that demonstrated the vasodilator effect of levosimendan on the pulmonary circulation, restoring right ventricular-arterial coupling as it increased right ventricular contractility concomitantly [10,11]. Acute PE-induced PH results from two main mechanisms: HighlightsBackground

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“…The mechanism of vasodilation by levosimendan may involve reduction of Ca 2+ sensitivity of contractile proteins in vascular smooth muscle, the lowering of intracellular free Ca 2+ , the potential inhibition of PDE III, and an opening of K + channels [89,90]. We have recently shown that levosimendan effectively and directly decreases the tone of IMA [91]. Therefore, levosimendan may be a cardiovascular protective agent by its relaxing action on IMA.…”

Section: Phosphodiesterase Inhibitorsmentioning

confidence: 99%