Effect of potassium channel opener pinacidil on the contractions elicited electrically or by noradrenaline in the human radial artery
2011
Gojkovic-Bukarica, Ljiljana | Savic, Natasa | Peric, Miodrag | Markovic-Lipkovski, Jasmina | Cirovic, Sanja | Kanjuh, Vladimir | Cvejic, Jelena | Atanackovic, Milica | Lešić, Aleksandar | Bumbasirevic, Marko | Heinle, Helmut
In order to discover an agent that can prevent spasm of the human radial artery, the aim of our study was to evaluate the effect of the K⁺ channel opener, pinacidil, on contractions in the radial artery. Contractions of the radial artery were evoked by exogenously applied noradrenaline or by electrical field stimulation (EFS, 20Hz, neurogenic). Pinacidil induced concentration-dependent inhibition of both EFS- and noradrenaline-evoked contractions of the radial artery. Glibenclamide, a selective blocker of ATP-sensitive K⁺ channels (Kir6.x containing subunit) antagonized in the same manner the pinacidil-induced inhibition of neurogenic contractions and contractions evoked by exogenous noradrenaline. The inhibition of pinacidil relaxation by tetraethylammonium (TEA), a blocker of Ca-sensitive K⁺ (KCₐ) channels, was more pronounced in EFS-contracted preparations. A blocker of voltage-sensitive K⁺ (KV) channels, 4-aminopyridine (4-AP), inhibited pinacidil relaxation only in EFS-contracted preparations. In order to test the presence of different K⁺ channels, immunohistochemistry of K⁺ channels expression in the radial artery was performed. The vascular wall of the human radial artery showed variable positivity with the following applied antibodies: Kv1.2, Kv1.3, Kir6.1, and KCₐ1.1. The antibodies against Kv1.6, Kv2.1, and Kir6.2 channel subunits were completely negative. These results suggest that the inhibitory effect of pinacidil on contractions of the human radial artery might be postsynaptic and associated with opening of smooth muscle Kir6.1-containing KATP channels. TEA- and 4-AP-sensitive K⁺ channels may also contribute to pinacidil effect in the human radial artery.
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