Effects of 2-nicotinamidethyl nitrate (SG-75) and/or nitroglycerin on systemic hemodynamics and coronary blood flow in conscious dogs.

The effect of 2-nicotinamidethyl nitrate (SG-75), a newly synthesized nitroester, on hemodynamics and coronary circulation was studied in conscious dogs, comparing it with nitroglycerin (NG). Dogs were previously instrumented with catheters in the aorta and left atrium and a Doppler flow probe on the left circumflex coronary artery. Percent increases in coronary flow rate were 11 (10 micrograms/kg), 20 (50 micrograms/kg), 71 (100 micrograms/kg) and 169% (200 micrograms/kg) in SG-75 and 3 (1 microgram/kg), 28 (5 microgram/kg), 65 (10 micrograms kg) and 99% (20 micrograms/kg) in NG, thus the dose ratio for an equivalent increase in mean coronary flow is about 10:1 between SG-75 and NG. The duration of coronary flow increase was also dose dependent and 2.1 min in 200 micrograms/kg SG-75 and 1.3 min in 20 micrograms/kg NG. Comparable changes in heart rate increase and pressure reduction were noted both in SG-75 and NG. The peculiar difference between two drugs was their time course of coronary flow increase: SG-75 showed monophasic increase while NG showed bipeaked increase in flow. The results suggest that the reflex increase in heart rate elicited by pressure drop after SG-75 did not influence the envelope of coronary flow increase such as observed upon NG administration.