Substance P contributes to rapidly adapting receptor responses to pulmonary venous congestion in rabbits

J Physiol. 1996 May 15;493 ( Pt 1)(Pt 1):229-38. doi: 10.1113/jphysiol.1996.sp021378.


1. This study tested the hypothesis that substance P stimulates rapidly adapting receptors (RARs), contributes to the increase in RAR activity produced by mild pulmonary congestion, and evokes an augmented response from RARs when combined with near-threshold levels of pulmonary congestion. 2. RAR activity, peak tracheal pressure, arterial blood pressure and left atrial pressure were measured in paralysed, anaesthetized and ventilated rabbits. Substance P was given i.v. in one-half log incremental doses to a maximum of 3 micrograms kg-1. Mild pulmonary congestion was produced by inflating a balloon in the left atrium to increase left atrial pressure by 5 mmHg. Near-threshold levels of pulmonary congestion 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 increased 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 responses to substance P and to mild pulmonary congestion. 4. Doses of substance P, which alone had no effect, stimulated the RARs when delivered during near-threshold levels of pulmonary congestion. 5. The findings suggest that substance P augments the stimulatory effect of mild pulmonary congestion on RAR activity, most probably by enhancing hydraulically induced microvascular leak.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Biphenyl Compounds / pharmacology
  • Blood Pressure / drug effects
  • Dose-Response Relationship, Drug
  • Male
  • Microcirculation / drug effects
  • Pulmonary Veins / drug effects*
  • Pulmonary Veins / metabolism
  • Rabbits
  • Receptors, Cell Surface / drug effects*
  • Receptors, Cell Surface / metabolism
  • Receptors, Tachykinin / antagonists & inhibitors
  • Receptors, Tachykinin / metabolism
  • Respiration / physiology
  • Substance P / pharmacology*
  • Tachykinins / pharmacology


  • Anti-Inflammatory Agents, Non-Steroidal
  • Biphenyl Compounds
  • Receptors, Cell Surface
  • Receptors, Tachykinin
  • Tachykinins
  • Substance P
  • CP 96345