PACAP-1-38 AS AN INHALED BRONCHODILATOR IN GUINEA-PIGS IN-VIVO

The effect on total pulmonary resistance (R-1) was examined for inhale d PACAP 1-38, PACAP 1-27 and VIP in anesthetized, ventilated guinea pi gs. Two minutes after inhalation, PACAP 1-38 (36 +/- 6%), PACAP 1-27 ( 42 +/- 9%) and VIP (48 +/- 19%) inhibited the increase in R-1 (% inhib ition of histamine-induced R-1 prior to inhalation) caused by histamin e IV, whereas the vehicle (-1 +/- 10%) did not. This inhibitory effect lasted five times longer for PACAP 1-38 (> 50 min) than for PACAP 1-2 7 and VIP (< 10 min). The inhaled peptides caused no sustained effects on heart rate or blood pressure. Infusion of PACAP 1-38 IV dose-depen dently inhibited the increase in R, caused by inhaled histamine and by carbachol IV. (C) 1998 Elsevier Science Inc.