Hydralazine-induced vasodilation involves opening of high conductance Ca2+-activated K+ channels

The purpose of this study was to investigate whether high conductance Ca2+-activated K+ channels (BKCa) are mediating the vasodilator action of hydralazine. In isolated porcine coronary arteries, hydralazine (1-300 mu M), like the K+ channel opener levcromakalim, preferentially relaxed contractions induced by K+ (20 mM) compared with K+ (80 mM). In addition, concentration-relaxation curves for hydralazine (pD(2) = 5.38 +/- 0.06; E-max = 85.9 +/- 3.6%) were shifted 10-fold to the right by the BKCa blockers tetraethylammonium (1 mM) and iberiotoxin (0.1 mu M). In contrast, nimodipine (a Ca2+-entry blocker), relaxed contractions induced by K+ (20 mM) and K+ (80 mM) equally and nimodipine-induced relaxations were neither antagonized by tetraethylammonium nor by iberiotoxin. In isolated perfused rat hearts, hydralazine (1 mu M) increased coronary flow by 28.8 +/- 2.7%. Iberiotoxin (0.1 mu M) suppressed this response by 82% (P < 0.05). In conscious, chronically catheterized rats the hypotensive response to hydralazine (0.6 mg kg(-1) min(-1)) was significantly reduced by 41% during infusion of iberiotoxin (0.1 mg kg(-1)). It is concluded, that opening of BKCa takes part in the mechanism whereby hydralazine produces vasodilation. (C) 1998 Elsevier Science B.V. All rights reserved.