Possible involvement of K+ channel opening to the interleukin-1 beta-induced inhibition of vascular smooth muscle contraction

We have previously shown that interleukin-1 beta relaxes vascular smooth mu scle by the NO-dependent and independent mechanisms (Takizawa et al.: fur. J. Pharmacol. 330: 143-150, 1997). In this study, we investigated the mecha nism of NO-independent relaxation. Treatment of the rat aorta with interleu kin-1 beta for 24 hr inhibited the high-K+ induced contraction by decreasin g cytosolic Ca2+ level ([Ca2+](i)). The relationship between [Ca2+](i) and tension in intact muscle and the pCa-tension curves in permeabilized muscle suggested that Ca2+ sensitivity of contractile element was not changed aft er the interleukin-1 beta-treatment. After a treatment with interleukin-1 b eta for 24 hr, contractile effects of phenylephrine (1 mu M-10 mu M) were m arkedly inhibited in the presence of L-NMMA (100 mu M) applied to inhibit N O synthesis. A blocker of ATP-sensitive K+ channel, glibenclamide (1 mu M), partially recovered the interleukin-1 beta-induced inhibition. In contrast , a blocker of Ca2+-activated K+ channel, charybdotoxin (0.1 mu M), was ine ffective. These results suggest that membrane hyperpolarization due to acti vation of ATP-sensitive K+ channels may partly be responsible for the NO-in dependent mechanism of interleukin-1 beta-induced inhibition of vascular sm ooth muscle contraction.