Protective effects of nipradilol, isosorbide dinitrate, and bunazosin on coronary artery constriction induced by intracoronary injection of acetylcholine in pigs.
OBJECTIVE
Protective effects of nipradilol, a newly synthesised vasodilating beta adrenoceptor antagonist, isosorbide dinitrate, and bunazosin on coronary artery constriction induced by intracoronary injection of acetylcholine were determined by coronary arteriography and compared in vivo in pigs.


METHODS
Acetylcholine (12.5, 25, 50, 100 and 200 micrograms) was given into the right coronary artery under left ventricular pacing to maintain constant systemic haemodynamics. Percentage narrowing of the major epicardial coronary artery was used as an indicator of constriction of the large coronary arteries, and the time required for the contrast medium to reach the posterior descending coronary artery from the ostium of the right coronary artery (blood flow delay) was used as an indicator of constriction of the small coronary arteries.


METHODS
15 farm pigs weighing 80 to 90 kg were used.


RESULTS
A marked blood flow delay of over 7.0 s (control: less than or equal to 1.8 s) with less than 34% narrowing of the epicardial major coronary artery was observed in 13 of 15 pigs with 12.5-50 micrograms of acetylcholine, and in the other two pigs with 100 micrograms of acetylcholine. When marked blood flow delay occurred, the perfused right ventricular myocardium became macroscopically anaemic (ischaemic). Over 75% narrowing of the major epicardial coronary artery was induced in six of the 15 pigs, and over 50% narrowing in 12, with marked blood flow delay with 100 to 200 micrograms of acetylcholine. However, after intracoronary infusion of 10 micrograms of nipradilol, acetylcholine induced narrowing in the epicardial major coronary artery was significantly reduced from 44-79% in control to 19-37% despite 200 micrograms of acetylcholine, though the time delay in coronary blood flow did not change significantly. By pretreatment with intracoronary isosorbide dinitrate (2.5 mg), the percent narrowing of the large coronary artery and the time delay in coronary blood flow were significantly reduced (narrowing from 32-84% to 10-27%; time delay from 7.6-41.6 s to 2.7-22.7 s). Pretreatment with intracoronary bunazosin, an alpha 1 adrenoceptor antagonist (100 micrograms), showed no protective effect on narrowing of the epicardial major coronary artery or blood flow delay.


CONCLUSIONS
Isosorbide dinitrate prevents coronary artery constriction induced by acetylcholine in swine. Nipradilol prevents large, but not small, coronary artery constriction, probably through a direct nitrate like vasodilating action.
Kawamura
A
A
Department of Internal Medicine, Kyoto University Hospital, Japan.
Fujiwara
H
H
Ishida
M
M
Takemura
G
G
Kida
M
M
Uegaito
T
T
Tanaka
M
M
Kawai
C
C
D000109:Acetylcholine / Q000037:antagonists & inhibitors*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D017023:Coronary Angiography; D003331:Coronary Vessels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007548:Isosorbide Dinitrate / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011799:Quinazolines; C018176:bunazosin; C036089:nipradilol; D007548:Isosorbide Dinitrate; D000109:Acetylcholine