Abstract

Glyceryl trinitrate (GTN, nitroglycerin) and pentrinitrol (PTN) lowered blood pressure in barbiturate-anesthetized dogs, cats and rats after i.v., intraportal vein (p.v.) and intraduodenal administration, and after oral dosing in conscious dogs and spontaneously hypertensive rats. Intravenously, GTN was more potent that PTN in each species. The separation in potency between GTN and PTN was less evident after p.v. administration, particularly in the dog, where p.v. dose-response curves to GTN and PTN were coinsident. GTN was more potent than PTN in reducing pulse pressure by the oral route in conscious dogs, although at equiactive doses PTN had a longer duration. PTN caused a greater and more persistent lowering of blood pressure than GTN after oral dosing in spontaneously hypertensive rats. In the dog, GTN and PTN had the same characteristic nitrate profile on coronary segmental resistance after i.v. or p.v. dosing, suggesting a similar mechanism by both routes. Although there is a wide separation in doses producing comparable effects by the various routes, these studies show GTN and PTN can exert their pharmacologic effects, specific for this class, by routes which necessitate passage through the liver.