Sidestream smoke exposure enhances rapidly adapting receptor responses to substance P in young guinea pigs.
We determined the effect of sidestream tobacco smoke (SS) exposure on responses of lung rapidly adapting receptors (RARs), peak tracheal pressure (Ptr), and arterial blood pressure (ABP) to substance P in young guinea pigs. Guinea pigs were exposed to SS or filtered air from day 8 to days 41-45 of life. They were then anesthetized and given three doses of intravenous substance P (1.56-4.94 nmol/kg). SS exposure augmented substance P-evoked increases in RAR activity (P = 0.029 by analysis of variance) but not substance P-evoked increases in peak Ptr or decreases in ABP. Neurokinin 1-receptor blockade (CP-96345, 400 nmol/kg) attenuated substance P-evoked increases in RAR activity (P = 0.001) and ABP (P = 0.009) but not in peak Ptr (P = 0.06). This chronic exposure to SS in young guinea pigs exaggerates RAR responsiveness to substance P. The findings may help explain the increased incidence of airway hyperresponsiveness and cough in children chronically exposed to environmental tobacco smoke.
Department of Internal Medicine and Pharmacology, University of California, Davis 95616, USA.
A C
AC
Bonham
K S
KS
Kott
J P
JP
Joad
D000222:Adaptation, Physiological / Q000187:drug effects; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1 / Q000187:drug effects*; D013268:Stimulation, Chemical; D013373:Substance P / Q000494:pharmacology; D013997:Time Factors; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D014132:Trachea / Q000187:drug effects / Q000502:physiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001713:Biphenyl Compounds; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; D014028:Tobacco Smoke Pollution; D013373:Substance P; C066892:CP 96345