Nitroglycerin and nitroprusside increase coronary blood flow in dogs by a mechanism independent of prostaglandin release.

The hypothesis that local release of vasodilator prostaglandins mediates, in part, the decrease in coronary resistance after nitroglycerin (NG) administration was tested. NG (60 micrograms/min) and nitroprusside (NP) (30 micrograms/min) were infused for 10 minutes into the left circumflex coronary artery of 9 open-chest, chloralose-anesthetized dogs before and after blockade of prostaglandin synthesis with indomethacin (5 mg/kg). Also, to eliminate the effects of reflex tachycardia on the responses to NG and NP, these experiments were repeated in 6 dogs with heart rate held constant by pacing. NG infusion into dogs without pacing resulted in a maximal increase in coronary blood flow of 55% and after 8 minutes of infusion an increase of 20%, from a baseline of 57 ml/min. NP infusion resulted in a maximal increase in blood flow of 89% and after 8 minutes an increase of 71%, from a baseline of 64 ml/min. In dogs with heart rate held constant, NG infusion caused a maximal increase in coronary artery blood flow of 132% and after 8 minutes of infusion an increase of 18%, from a baseline of 48 ml/min; NP infusion resulted in increase from 51 ml/min of 132% and 62%, respectively. In neither group of dogs did indomethacin significantly change the increases in coronary blood flow or decreases in coronary resistance to NG or NP. Thus, both NG and NP, when infused into the coronary artery of dogs, cause increases in coronary blood flow and decreases in coronary resistance by a mechanism which is independent of prostaglandin release.