DIFFERENTIAL-EFFECTS OF AGENTS ON BRONCHIAL AND VASCULAR TONE AND LUNG WEIGHT IN THE RAT ISOLATED-PERFUSED LUNG

A ventilated perfused model of rat lung is described enabling continuo us simultaneous measurement of pulmonary perfusion pressure (PPP), pul monary inflation pressure (PIP) and lung weight. The preparation was s table for 2 h before oedema formation commenced. Phenylephrine injecte d into the pulmonary artery produced selective increases in PPP (ED(50 ) 4.0+/-0.7 nmol, n=5) without affecting airway tone or lung weight. C arbachol under basal perfusion conditions caused bronchoconstriction ( ED(50) 4.25+/-0.4 nmol, n=7) without affecting PPP and lung weight. Br adykinin (BK) caused increases in PPP (ED(50) 22+/-3 nmol, n=8), lung weight and PIP (ED(50) 35.6+/-3.6 nmol, n=8). Low doses of BK (25-50 n mol) caused increases in lung weight which were reversible. Higher dos es (100-200 pmol) caused irreversible increases in lung weight which a lbumin-bound dye infusion showed were associated with albumin accumula tion. Manipulation of venous outflow pressure revealed that the change s in lung weight induced by BK were potentially explicable as sequelae of vascular hydrostatic pressure changes possibly resulting from veno constriction. It is concluded that this model is useful for studying d rug actions on bronchial tone, pulmonary vasculature tone and vascular permeability.