SUBSTANCE-P CONTRIBUTES TO RAPIDLY ADAPTING RECEPTOR RESPONSES TO PULMONARY VENOUS CONGESTION IN RABBITS

1. This study tested the hypothesis that substance P stimulates rapidl y adapting receptors (RARs), contributes to the increase in RAR activi ty produced by mild pulmonary congestion, and evokes an augmented resp onse from RARs when combined with near-threshold levels of pulmonary c ongestion. 2. RAR activity, peak tracheal pressure, arterial blood pre ssure and left atrial pressure were measured in paralysed, anaesthetiz ed and ventilated rabbits. Substance P was given I.V. in one-half log incremental doses to a maximum of 3 mu g kg(-1). Mild pulmonary conges tion was produced by inflating a balloon in the left atrium to increas e left atrial pressure by 5 mmHg. Near-threshold levels of pulmonary c ongestion were produced by increasing left atrial pressure by 2 mmHg. 3. Substance P produced dose-dependent increases in RAR activity. The highest dose given increased the activity from 1.3 +/- 0.5 to 11.0 +/- 3.1 impulses bin(-1). Increases in left atrial pressure of 5 mmHg inc reased RAR activity from 3.8 +/- 1.4 to 14.7 +/- 3.9 impulses bin(-1) Blockade of NK1 receptors with CP 96345 significantly attenuated RAR r esponses to substance P and to mild pulmonary congestion. 4. Doses of substance P, which alone had no effect, stimulated the RARs when deliv ered during near-threshold levels of pulmonary congestion. 5. The find ings suggest that substance P augments the stimulatory effect of mild pulmonary congestion on RAR activity, most probably by enhancing hydra ulically induced microvascular leak.