Substance P contributes to rapidly adapting receptor responses to pulmonary venous congestion in rabbits.
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.
Bonham
A C
AC
Department of Internal Medicine, University of California, Davis 95616, USA.
Kott
K S
KS
Ravi
K
K
Kappagoda
C T
CT
Joad
J P
JP
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D011667:Pulmonary Veins / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors / Q000378:metabolism; D012119:Respiration / Q000502:physiology; D013373:Substance P / Q000494:pharmacology*; D015320:Tachykinins / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001713:Biphenyl Compounds; D011956:Receptors, Cell Surface; D018039:Receptors, Tachykinin; D015320:Tachykinins; D013373:Substance P; C066892:CP 96345