The effect of
KRN2391 [N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide monomethanesulfonate] on the cardiovascular system and on myocardial oxygen consumption was compared with that of
nicorandil and
nifedipine in anesthetized dogs.
Intravenous administration of
KRN2391 (3-30 micrograms/kg) and
nifedipine (1 and 3 micrograms/kg) decreased mean aortic blood pressure and total peripheral vascular resistance, and increased coronary blood flow, cardiac output and stroke volume. Heart rate was not significantly affected by
KRN2391, but slightly increased by 1 microgram/kg of
nifedipine.
Nicorandil (100 and 300 micrograms/kg, intravenously) decreased mean aortic blood pressure, cardiac output, stroke volume and total peripheral vascular resistance, but did not affect heart rate.
Nicorandil also showed a tendency to decrease coronary blood flow after an initial increase. All drugs tested decreased the difference in
oxygen concentration between arterial and coronary sinus blood, indicating that these drugs increased the
oxygen supply to the heart. Myocardial oxygen consumption was significantly decreased by more than 10 micrograms/kg of
KRN2391, but was not affected by
nifedipine.
Nicorandil showed a tendency to decrease the myocardial oxygen consumption, though not significantly. Thus,
KRN2391 may be useful to treat
ischemic heart disease, because it increases the coronary blood flow and the
oxygen supply to the heart, and decreases the afterload and the myocardial oxygen consumption.