US EPA

2251135 

Technical Report 

Comparative Studies on the Mechanism of Antianginal Action of Trolnitrate Phosphate and Nitroglycerin in Animals 

Scriabine, A; Mcshane, WK 

1965 

NIOSH/00130049 

5 

3 

143-152 

English 

4284102 

The mechanism of antianginal action of nitroglycerin (55630) and trolnitrate-phosphate (588421) was studied in rabbit aortic tissue and in anesthetized dogs. Strips of rabbit aorta were suspended in Krebs Henseleit solution and treated with 0.00005 milligrams per milliliter (mg/ml) epinephrine (51434) or angiotensinamide (53736) to produce contractions. Nitroglycerin or trolnitrate-phosphate was then added in concentrations of 0.000001 to 0.01mg/ml, and the effect on contractions was observed. Anesthetized dogs were given an intravenous infusion of 5, 20, or 80 micrograms per kilogram (microg/kg) nitroglycerin or 80, 320, or 1280microg/kg trolnitrate-phosphate. Cardiac work, coronary and total peripheral vascular resistance, blood pressure, cardiac output, myocardial oxygen uptake, and coronary blood flow were measured 1 minute after nitroglycerin and 10 minutes after trolnitrate-phosphate, and compared to values from untreated controls. At 0.001mg/ml, nitroglycerin produced almost complete blockage of contractions produced by either agent. Trolnitrate-phosphate also blocked contractions. However, nitroglycerin was 35 times more potent against epinephrine induced contractions and 11 times more potent against angiotensinamide induced contractions. Dogs receiving the highest dose of either drug showed significantly reduced values for all parameters except coronary blood flow. The effects of nitroglycerin were immediate and lasted less than 5 minutes. Maximal effects of trolnitrate-phosphate were reached in 4 to 10 minutes and lasted up to 20 minutes. The authors conclude that peripheral vasodilator activity is responsible for the therapeutic efficacy of these antianginal agents.