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 continuous simultaneous measurement of pulmonary perfusion pressure (PPP), pulmonary inflation pressure (PIP) and lung weight. The preparation was stable for 2h before oedema formation commenced. Phenylephrine injected into the pulmonary artery produced selective increases in PPP (ED50 4.0 +/- 0.7 nmol, n = 5) without affecting airway tone or lung weight. Carbachol under basal perfusion conditions caused bronchoconstriction (ED50 4.25 +/- 0.4 nmol, n = 7) without affecting PPP and lung weight. Bradykinin (BK) caused increases in PPP (ED50 22 +/- 3 nmol, n = 8), lung weight and PIP (ED50 35.6 +/- 3.6 nmol, n = 8). Low doses of BK (25-50 nmol) caused increases in lung weight which were reversible. Higher doses (100-200 pmol) caused irreversible increases in lung weight which albumin-bound dye infusion showed were associated with albumin accumulation. Manipulation of venous outflow pressure revealed that the changes in lung weight induced by BK were potentially explicable as sequelae of vascular hydrostatic pressure changes possibly resulting from venoconstriction. It is concluded that this model is useful for studying drug actions on bronchial tone, pulmonary vasculature tone and vascular permeability.