VASODILATING EFFECTS OF TETRAZEPAM IN ISOLATED VASCULAR SMOOTH MUSCLES - COMPARISON WITH CROMAKALIM AND DILTIAZEM

The vasodilating effects of tetrazepam (1,4-benzodiazepine derivative) were studied and compared with those of the K-channel activator, crom akalim and the Ca-channel blocker, diltiazem, in rat aorta smooth musc le and on the spontaneous contractile activity of the rat portal vein. In the aorta, tetrazepam (3 X 10(-7) - 10(-4) M) and diltiazem (10(-8 ) - 3 X 10(-6) M) concentration-dependently relaxed aortic rings contr acted by 30 mM as well as 80 mM KCl. Although cromakalim (10(-8) - 3 X 10(-6) M) concentration-dependently relaxed aortic rings contracted b y 30 mM KCl, it did not relax those contrated by 80 mM KCl. In the pre sence of the ATP-sensitive K-channel blocker, glibenclamide (10(-6) an d 3 X 10(-6) M), 30 mM KCl concentration-response curves for the relax ant effect of tetrazepam and diltiazem were unaffected but cromakalim caused a progressive shift of these curves upwards. In the portal vein , tetrazepam inhibited spontaneous contractions, decreased amplitude a nd increased frequency. Similar behaviour was shown with diltiazem (10 (-8) - 10(-5) M) and in both cases, pre-treatment with glibenclamide ( 10(-6) M) was ineffective. Although cromakalim (10(-5) - 10(-6) M) dec reased both amplitude and frequency, this effect was blocked by gliben clamide. These results indicate that the vasodilator action of tetraze pam is not mediated to the opening of ATP-sensitive K-channels, unlike cromakalim. This may be mediated, like those of diltiazem, by the blo ckade of calcium movements across the cell membrane. (C) 1997 The Ital ian Pharmacological Society.