Augmentation of parasympathetic contraction in tracheal and bronchial airways by PGF2 alpha in situ

Abstract
The effect of exogenous prostaglandin F2.alpha. (PGF2.alpha.) on airway smooth muscle contraction caused by parasympathetic stimulation was studied in 22 mongrel dogs in situ. Voltage (0-30 V, constant 20 Hz) and frequency-response (0-25 Hz, 25 V) curves were generated by stimulating the cut ends of both cervical vagus nerves. Airway response was measured isometrically as active tension (AT) in the segment of cervical trachea and as change in airway resistance (RL) and dynamic compliance (Cdyn) in bronchial airways. After 5 mg/kg i.v. indomethacin (1 h), a cumulative frequency-response curve was generated in 9 animals by electrical stimulation of the vagus nerves at 15-s intervals. Reproducibility was demonstrated by generating a 2nd curve 7 min later. A 3rd frequency-response curve was generated during active contraction of the airway caused by continuous i.v. infusion of 10 .mu.g .cntdot. kg-1 .cntdot. min-1 PGF2.alpha.. Additional frequency-response studies were generated 15 and 30 min after PGF2.alpha., when airway contractile response (.DELTA.RL = +2.8 .+-. 0.65 cmH2O .cntdot. 1-1 .cntdot. s; .DELTA.Cdyn = 0.0259 .+-. 0.007 1/cmH2O) returned to base line. Substantial augmentation of AT, RL and Cdyn responses was demonstrated in every animal studied (P < 0.01 for all points > 8 Hz) 15 min after PGF2.alpha.. At 30 min, response did not differ from initial base-line control. In 4 animals receiving sham infusion, all frequency-response curves were identical. PGF2.alpha. augments the response to vagus nerve stimulation in tracheal and bronchial airways. Augmentation does not depend on PGF2.alpha.-induced active tone.