title: Acute cardiovascular and pulmonary effects of intravenous and aerosolized amiloride in the dog.
abstract: Active Na+ absorption by the epithelia that line the airways can drive volume from the airway surface. Exposure of the lumen-facing surface of airway epithelia to amiloride inhibits Na+ transport. Consequently, aerosolized amiloride may help hydrate the desiccated surface liquid that characterizes lung diseases such as cystic fibrosis. We studied the acute cardiovascular and pulmonary effects of amiloride in anesthetized dogs. Intravenous amiloride reduced blood pressure and increased ventilation frequency and airways resistance of the dog. The effects were dose-related (ED50 = 1.3 X 10(-6) mol/kg), resembled those of injected histamine, and were antagonized by methapyrilene. These results were compatible with the release of endogenous histamine by amiloride, but the graded dose-effect relationship for amiloride differed from the quantal relationship induced by the prototypical releaser, 48/80. Aerosolization of a Ringer's solution that was nearly saturated with amiloride deposited, in upper airway surface liquid, drug concentrations which in previous studies, were sufficient to inhibit Na+ transport by canine airways (ED50 approximately 10(-6) M). Cardiovascular function, airways resistance, and indices of pulmonary tissue water, gas exchange, and perfusion were not affected. Since circulating amiloride after aerosolization was estimated to fall below the concentration that induced vasodepression and correct circled bronchoconstriction after intravenous injection, we conclude that the potency of aerosolized amiloride to induce acute effects in tissues other than airway epithelia is no greater than that of intravenous drug.
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000403:Airway Resistance / Q000187:drug effects; D000584:Amiloride / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D004285:Dogs; D004573:Electrolytes / Q000097:blood; D005260:Female; D007275:Injections, Intravenous; D008168:Lung / Q000187:drug effects*; D008297:Male; D012119:Respiration / Q000187:drug effects
chemical_list: D000336:Aerosols; D004573:Electrolytes; D000584:Amiloride