PULMONARY VASODILATOR RESPONSES TO NICARDIPINE - COMPARISON WITH OTHER VASODILATORS

Objectives: To determine the direct effect of nicardipine on the pulmo nary vascular bed of the intact-chest, spontaneously breathing cat, an d to compare its effectiveness as a pulmonary vasodilator with the eff ectiveness of isoproterenol, nitroglycerin, and sodium nitroprusside. Design: Prospective, controlled animal study. Each animal received all drugs in random order. Setting: Animal laboratory at a university. Su bjects: Experiments were performed in vivo in ten intact-chest, sponta neously breathing cats with controlled pulmonary blood flow and consta nt left atrial pressure, during conditions of increased pulmonary vasc ular tone. Interventions: Five animals received intralobar injections of nicardipine (0.1 to 100 mu g), nitroglycerin (0.1 to 10 mu g), sodi um nitroprusside (0.1 to 100 mu g), and isoproterenol (0.01 to 1 mu g) . Injections were made only when lobar arterial pressure had returned to baseline value. In another five animals, nicardipine, nitroglycerin , and sodium nitroprusside were administered intravenously as a contin uous drug infusion in incremental doses titrated to produce a 20% redu ction in mean systemic arterial pressure. Each dose was infused until lobar and systemic arterial pressures stabilized. A minimum, 30-min in terval was allowed between the infusions of these drugs. Measurements and Main Results: When pulmonary vascular tone was increased with a th romboxane A, mimetic (analog), U46619 (a stable prostaglandin endopero xide analog), intralobar injections of nicardipine caused dose-related decreases in lobar arterial pressure without affecting left atrial pr essure. When compared with the other vasodilator agents, the order of potency was isoproterenol much greater than nitroglycerin > nicardipin e = sodium nitroprusside. Isoproterenol reduced mean systemic arterial pressure 10 to 100 times greater than nitroglycerin, nicardipine, or sodium nitroprusside. However, there were no significant differences b etween the latter three drugs in producing a decrease in mean systemic arterial pressure. When infused intravenously, nitroglycerin caused t he largest amount of pulmonary vasodilation for a given amount of syst emic vasodilation. There were no significant differences between the p ulmonary vasodilator responses of nicardipine and sodium nitroprusside . Conclusions: In this feline model of increased pulmonary vascular re sistance, nicardipine exerts a direct vasodilator effect in vivo on th e pulmonary vascular bed. Nicardipine, nitroglycerin, and sodium nitro prusside caused similar decreases in systemic arterial pressure. Howev er, the pulmonary vasodilator effect was greater with nitroglycerin, w hich suggests that nitroglycerin is more vasoselective for the pulmona ry vascular bed than nicardipine or sodium nitroprusside.