COMPARISONS OF THE EFFECTS OF NICORANDIL, PINACIDIL, NICARDIPINE AND NITROGLYCERIN ON CORONARY VESSELS IN THE CONSCIOUS DOG - ROLE OF THE ENDOTHELIUM

1 The vasodilator properties of nicorandil on large and small coronary arteries were compared to those of nicardipine, pinacidil, nitroglyce rin and acetylcholine in six conscious dogs. 2 Intravenous bolus injec tions of acetylcholine (0.1 mu g kg(-1)), nitroglycerin (0.3-3 mu g kg (-1)), pinacidil (10-100 mu g kg(-1)), nicardipine (3-30 mu g kg(-1)) and nicorandil (10-100 mu g kg(-1)) dose-dependently increased circumf lex coronary artery diameter and decreased coronary vascular resistanc e, indicating vasodilator effects on both conduit and resistance coron ary arteries. 3 Three days after removal of the endothelium of the cir cumflex coronary artery (balloon angioplasty), pinacidil- and nicardip ine-induced dilatation of large coronary arteries was greatly reduced (both - 76%, P<0.01) whereas that produced by nitroglycerin and nicora ndil was decreased only slightly and to a similar extent for both drug s (- 19%, P<0.01 and - 28%, P<0.05, respectively). 4 Thus in conscious dogs, nicardipine- and pinacidil-induced dilatation of large coronary arteries is endothelium-dependent. In contrast, the vasodilator effec ts of nitroglycerin and nicorandil on conduit vessels are endothelium- independent. 5 Finally, our results demonstrate that nicorandil dilate s the large coronary arteries through its nitrate-like action and that the ATP-potassium channel opening properties of the drug are not invo lved in this effect in the conscious dog.