CHARACTERISTICS OF THE CONTRACTILE RESPONSE OF RABBIT AORTA PRODUCED BY CROMAKALIM IN CALCIUM-FREE SOLUTION

1 The effect of potassium channel opening compounds has been investigated in the smooth muscle of rabbit aorta under Ca-free conditions. Examination of the characteristics of the response has been performed using cromakalim as the prototype compound. 2 In order of potency, Ro 31-6930, cromakalim, minoxidil sulphate and pinacidil each produced a contraction in rabbit aortic strips bathed in Ca-free MOPS-buffered physiological salt solution (PSS). In contrast, forskolin, glyceryl trinitrate and nifedipine each failed to increase tension under identical conditions. Cromakalim also evoked contraction of bovine trachealis muscle bathed in Ca-free PSS. 3 The contractile response to cromakalim in rabbit aortic strips was of delayed onset (15-20 min) and reached a plateau after approximately 120 rtiin (1.8 g maximum with 1 muM cromakalim). No cromakalim-induced tension changes were observed in either 1 mM or 2.5 mm Ca-containing PSS. 4 Raising the [KCl] of the Ca-free PSS to 65.9 mm fully inhibited the cromakalim-induced contraction in rabbit aortic strips. In addition, pretreatment of aortic strips with the sulphonylurea glibenclamide antagonized the subsequent mechanical response to cromakalim. 5 In Ca-free PSS, cromakalim (1 muM) stimulated K-42-efflux with a time-course corresponding to the contractile event. Glibenclamide (1 muM) inhibited this cromakalim-induced K-42-efflux. 6 In sharp microelectrode studies in bovine trachealis, cromakalim (10 muM) produced a sustained membrane hyperpolarization in normal PSS. In contrast, the cromakalim-induced hyperpolarization in Ca-free PSS was not sustained. The fading of the hyperpolarization was temporally correlated with the increase in tension under these experimental conditions. 7 It is concluded that the K-channel opener-induced smooth muscle contractile response revealed in Ca-free PSS is the consequence of K-channel opening. The nature of the detailed mechanism which underlies this contractile phenomenon remains to be determined.