Coronary Vasorelaxant Effect of Levosimendan, a New Inodilator with Calcium-Sensitizing Properties
We examined the action of levosimendan, a new Ca-sensitizing inodilator, on isolated porcine coronary arteries. Vessel rings were studied in isometric myographs. Arterial cyclic adenosine monophosphate (cAMP) levels were determined by radioimmunoassay. Levosimendan (10−10 M) completely relaxed arter...
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Veröffentlicht in: | Journal of cardiovascular pharmacology 1998-05, Vol.31 (5), p.741-749 |
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Zusammenfassung: | We examined the action of levosimendan, a new Ca-sensitizing inodilator, on isolated porcine coronary arteries. Vessel rings were studied in isometric myographs. Arterial cyclic adenosine monophosphate (cAMP) levels were determined by radioimmunoassay. Levosimendan (10−10 M) completely relaxed arteries preconstricted by prostaglandin F2α (PGF2α) with a pD2 (−logEC50) value of 3.99 ± 0.05 (n = 6-9 in all experiments). Pretreatment with levosimendan also prevented contraction induced by PGF2α. The vasorelaxation produced by levosimendan (10−10 M) was not attenuated by removal of the endothelium. Levosimendan (10−10 M) relaxed contractions induced by 30 mM K as well as 80 mM K, whereas the K channel opener levcromakalim selectively relaxed contraction induced by 30 mM K. Neither the cyclooxy-genase inhibitor indomethacin nor the β-adrenoceptor blocker propranolol influenced levosimendan-induced vasorelaxation. The Ca-entry blocker isradipine failed to relax arteries precontracted by endothelin-1 in Ca-free/EGTA medium. However, levosimendan (10−3 × 10 M) completely relaxed endothelin-1-induced contractions in this medium. Levosimendan potentiated the relaxant effect of a cAMP-stimulating drug, isoprenaline, but also that of nitroglycerin and isradipine. At a maximal effective concentration, it increased arterial tissue contents of cAMP twofold. In conclusion, levosimendan produces coronary vasorelaxation by a mechanism that seems to be endothelium independent and not mediated by K channel opening, Ca-entry blockade, release of cyclooxygenase products, or β-adrenoceptor stimulation. Accumulation of cAMP may possibly participate in vasorelaxation at high concentrations of levosimendan, but a cAMP-independent mechanism seems to be involved at lower concentrations. |
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ISSN: | 0160-2446 1533-4023 |
DOI: | 10.1097/00005344-199805000-00013 |