Abstract
1 We characterized the vasoactive effects of OR-1896, the long-lived metabolite of the inodilator levosimendan, in coronary and skeletal muscle microvessels. 2 The effect of OR-1896 on isolated, pressurized (80 mmHg) rat coronary and gracilis muscle arteriole (∼150 μm) diameters was investigated by videomicroscopy. 3 OR-1896 elicited concentration-dependent (1 nM-10 μM) dilations in coronary (maximal dilation: 66±6%, relative to that in Ca 2+-free solutions; pD 2: 7.16±0.42) and gracilis muscle arterioles (maximal dilation: 73±4%; pD 2: 6.71±0.42), these dilations proving comparable to those induced by levosimendan (1 nM-10 μM) in coronary (maximal dilation: 83±6%; pD 2: 7.06±0.14) and gracilis muscle arterioles (maximal dilation: 73±12%; pD 2: 7.05±0.1). 4 The maximal dilations in response to OR-1896 were significantly (P<0.05) attenuated by the nonselective K + channel inhibitor tetraethylammonium (1 mM) in coronary (to 34±9%) and gracilis muscle arterioles (to 28±6%). 5 Glibenclamide (5 or 10 μM), a selective ATP-sensitive K + channel (K ATP) blocker, elicited a greater reduction of OR-1896-induced dilations in skeletal muscle arterioles than in coronary microvessels. 6 Conversely, the selective inhibition of the large conductance Ca 2+-activated K + channels (BK Ca) with iberiotoxin (100 nM) significantly reduced the OR-1896-induced maximal dilation in coronary arterioles (to 21±6%), but was ineffective in skeletal muscle arterioles (72±8%). 7 Accordingly, OR-1896 elicits a substantial vasodilation in coronary and skeletal muscle arterioles, by activating primarily BK Ca and K ATP channels, respectively, and it is suggested that OR-1896 contributes to the long-term hemodynamic effects of levosimendan.
Original language | English (US) |
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Pages (from-to) | 696-702 |
Number of pages | 7 |
Journal | British Journal of Pharmacology |
Volume | 148 |
Issue number | 5 |
DOIs | |
State | Published - Jul 5 2006 |
Externally published | Yes |
Keywords
- Coronary
- K channels
- Levosimendan
- Microvessel
- OR-1896
- Skeletal muscle
- Vasodilation
ASJC Scopus subject areas
- Pharmacology