PACAP 1-38 as an inhaled bronchodilator in guinea pigs in vivo.
The effect on total pulmonary resistance (R1) was examined for inhaled PACAP 1-38, PACAP 1-27 and VIP in anesthetized, ventilated guinea pigs. Two minutes after inhalation, PACAP 1-38 (36 +/- 6%), PACAP 1-27 (42 +/- 9%) and VIP (48 +/- 19%) inhibited the increase in R1 (% inhibition of histamine-induced R1 prior to inhalation) caused by histamine i.v., whereas the vehicle (-1 +/- 10%) did not. This inhibitory effect lasted five times longer for PACAP 1-38 (> 50 min) than for PACAP 1-27 and VIP (< 10 min). The inhaled peptides caused no sustained effects on heart rate or blood pressure. Infusion of PACAP 1-38 i.v. dose-dependently inhibited the increase in R1 caused by inhaled histamine and by carbachol i.v..
Lindén
A
A
Cardiovascular Research Institute, University of California San Francisco 94143-0130, USA.
Cardell
L O
LO
Yoshihara
S
S
Stjärne
P
P
Nadel
J A
JA
D000280:Administration, Inhalation; D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D008168:Lung / Q000187:drug effects*; D008297:Male; D009479:Neuropeptides / Q000008:administration & dosage / Q000494:pharmacology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014660:Vasoactive Intestinal Peptide / Q000008:administration & dosage / Q000494:pharmacology*
D001993:Bronchodilator Agents; D009479:Neuropeptides; D010446:Peptide Fragments; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; C108046:pituitary adenylate cyclase-activating-peptide (1-38), pig; D014660:Vasoactive Intestinal Peptide; D006632:Histamine; D002217:Carbachol