A COMPARISON OF THE RELAXANT EFFECTS OF PINACIDIL IN RABBIT RENAL AND MESENTERIC-ARTERY

1. The relaxant effects of pinacidil were compared in isolated rabbit renal and mesenteric artery. 2. Pinacidil (10 nm-300 mu M) relaxed renal and mesenteric arterial rings precontracted with phenylephrine with pD(2) values of 5.11 +/- 0.03 and 6.27 +/- 0.04, respectively. 3. The inhibitory effect of pinacidil on the rabbit mesenteric artery was competitively antagonized by glibenclamide (1-10 mu M). The calculated pK(B) value was 6.37 +/- 0.04. On the renal artery, glibenclamide (2-20 mu M) did not significantly affect pinacidil-induced relaxation (P > 0.05). 4. Tetraethylammonium (TEA, 1-10 mM) competitively antagonized the pinacaidil induced relaxation of the rabbit renal artery. The pK(B) value was 3.22 +/- 0.08. On the mesenteric artery TEA antagonized the effect of pinacidil in a noncompetitive manner. 5. The concentration-response curves for pinacidil on the rabbit renal and mesenteric artery were not affected by apamin (0.1 mu M). 6. It is concluded that ATP-sensitive K+ channels (K-ATP) are not involved in pinacidil action on the rabbit renal artery. On the contrary, K-ATP are probably major sites of pinacidil action on the rabbit mesenteric artery.