Neonatal capsaicin treatment alters basal pulmonary mechanics and response to methacholine in F344 rats.
Full methacholine dose-response curves were performed on anesthetized tracheostomized Fischer 344 adult rats treated neonatally with capsaicin (50 mg/kg) or with vehicle alone. Capsaicin, the hot extract of pepper, releases substance P (SP) from nonmyelinated sensory nerve endings and causes acute bronchoconstriction and airway microvascular leakiness. Chronic treatment with capsaicin leads to depletion of SP and other tachykinins from afferent C-fibers and can therefore be used as a tool to investigate the contribution of SP innervation to airway responses. The rats (9 controls and 6 treated with capsaicin) were paralyzed with succinylcholine and mechanically ventilated at a constant tidal volume and frequency. Airway resistance (RL) and dynamic compliance (Cdyn) were determined at each dose of methacholine from measurements of volume, flow, and transpulmonary pressure. Capsaicin-treated rats were found to have a significantly reduced baseline RL [0.150 +/- 0.039 (SD) vs. 0.225 +/- 0.050 cmH2O.ml-1.s, P = 0.009] and a correspondingly significantly elevated Cdyn (0.371 +/- 0.084 vs. 0.268 +/- 0.053 ml/cmH2O, P = 0.012). There was no significant difference in sensitivity to methacholine, but the maximal response to methacholine was significantly greater in the capsaicin-treated rats. In terms of RL, the maximal response for capsaicin-treated rats was 6.03 x baseline +/- 0.98 vs. 4.30 x baseline +/- 1.80 (P = 0.05) for controls, and for Cdyn changes the maximal decrease was 5.75 x baseline +/- 1.22 vs. 3.83 +/- 0.69 (P = 0.002). The observed differences in RL and Cdyn coupled with the differences in maximal responses can be attributed to the selective destruction of a subpopulation of pulmonary afferent C-fibers.(ABSTRACT TRUNCATED AT 250 WORDS)
App
E M
EM
Pulmonary Defense Group, University of Alberta, Edmonton, Canada.
De Sanctis
G T
GT
Green
F H
FH
Hulbert
W C
WC
Rubin
B K
BK
Remmers
J E
JE
King
M
M
D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D000403:Airway Resistance / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001980:Bronchi / Q000187:drug effects / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage / Q000494:pharmacology*; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D015656:Respiratory Mechanics / Q000187:drug effects* / Q000502:physiology; D013373:Substance P / Q000502:physiology
D016210:Methacholine Chloride; D013373:Substance P; D002211:Capsaicin