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, nitroglycerin and acetylcholine in six conscious dogs. 2. Intravenous bolus injections of acetylcholine (0.1 micrograms kg-1), nitroglycerin (0.3-3 micrograms kg-1), pinacidil (10-100 micrograms kg-1), nicardipine (3-30 micrograms kg-1) and nicorandil (10-100 micrograms kg-1) dose-dependently increased circumflex coronary artery diameter and decreased coronary vascular resistance, indicating vasodilator effects on both conduit and resistance coronary arteries. 3. Three days after removal of the endothelium of the circumflex coronary artery (balloon angioplasty), pinacidil- and nicardipine-induced dilation of large coronary arteries was greatly reduced (both -76%, P < 0.01) whereas that produced by nitroglycerin and nicorandil was decreased only slightly and to a similar extent for both drugs (-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 effects of nitroglycerin and nicorandil on conduit vessels are endothelium-independent. 5. Finally, our results demonstrate that nicorandil dilates the large coronary arteries through its nitrate-like action and that the ATP-potassium channel opening properties of the drug are not involved in this effect in the conscious dog.
Ghaleh
B
B
Département de Pharmacologie, Faculté de Médecine Paris-Sud, Le Kremlin Bicêtre, France.
Dubois-Randé
J L
JL
Hittinger
L
L
Giudicelli
J F
JF
Berdeaux
A
A
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects*; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects*; D006146:Guanidines / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D009529:Nicardipine / Q000494:pharmacology; D020108:Nicorandil; D005996:Nitroglycerin / Q000494:pharmacology; D020110:Pinacidil; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D006146:Guanidines; D014665:Vasodilator Agents; D009536:Niacinamide; D020108:Nicorandil; D020110:Pinacidil; D009529:Nicardipine; D005996:Nitroglycerin; D000109:Acetylcholine